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    • A commentary on the discrepancy between blood and tumour BRCA testing: An open question.
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    Related:

    Press Release: Myriad Genetics Advances Precision Oncology with New Precise™ Solutions, Combines Genetic Insights from Multiple Tests to Guide Treatment Decisions and Improve Patient Care. (Myriad Genetics)

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    Related:

    Research news: NHS gene testing misses half of people at risk of cancer, study warns. (Sky News)

    • Functional Analysis Identifies Damaging CHEK2 Missense Variants Associated with Increased Cancer Risk.
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    • Letter to the Editor: CHEK2 I157T - Pluto Among Numerous Low-Risk Genetic Factors Requiring Discharge From a Range of Pathogenic Variants?
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    Related:

    Guideline:

    Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology.

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    Related:

    Commentary:

    Coiled-Coil Domain: Uncoiling Tumor Suppression by BRCA1.

    • Closing the gap: Systematic integration of multiplexed functional data resolves variants of uncertain significance in BRCA1, TP53, and PTEN.
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    Related:

    Press: Most Genetic Counselors Encounter Discrepant Variant Classifications, Must Work Out Interpretations. (Precision Oncology News)

    • Assessing BRCA1 activity in DNA damage repair using human induced pluripotent stem cells as an approach to assist classification of BRCA1 variants of uncertain significance.
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    • Press, Conference report

    Related:

    Original research:

    Closing the gap: Systematic integration of multiplexed functional data resolves variants of uncertain significance in BRCA1, TP53, and PTEN.

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    Related:

    News: BRCA2 Variants of Unknown Significance Reclassified Through Functional Data Additions (Precision Oncology News)

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    Related:

    Letter, Commentary:

    RNA-Seq Analysis Is a Useful Tool in Variant Classification.

    Letter, Reply:

    Reply to R. Karam et al.

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    • Letter
    • Functional categorization of BRCA1 variants of uncertain clinical significance in homologous recombination repair complementation assays.
    • Bouwman P, van der Heijden I, van der Gulden H, de Bruijn R, Braspenning ME, Moghadasi S, Wessels LFA, Segers K, Badoer C, Vandernoot I, Hilbert P, Storm K, Blaumeiser B, Claes KBM, Seneca S, Michils G, van den Ouweland A, Collée JM, van der Stoep N, Blok MJ, Bleeker FE, Hogervorst FBL, Mensenkamp AR, van der Hout AH, Oosterwijk JC, van der Luijt RB, Koudijs MJ, Vreeswijk MPG, Jonkers J.
    • Clin Cancer Res. 2020 Jun 16:clincanres.0255.2020. doi: 10.1158/1078-0432.CCR-20-0255. Epub ahead of print.
    • Sequencing technology status of BRCA1/2 testing in Latin American Countries.
    • Solano AR, Palmero EI, Delgado L, Carraro DM, Ortíz-López R, Carranza CL, Santamaria C, Cifuentes L, Jara Sosa LE, Toland AE.
    • NPJ Genom Med. 2020 Jun 2;5(1):22. doi: 10.1038/s41525-020-0126-3.

    Duplicate of:

    • Sequencing technology status of BRCA1/2 testing in Latin American Countries.
    • Solano AR, Palmero EI, Delgado L, Carraro DM, Ortíz-López R, Carranza CL, Santamaria C, Cifuentes L, Jara Sosa LE, Toland AE.
    • NPJ Genom Med. 2020 Jun 2;5:22. doi: 10.1038/s41525-020-0126-3.
    • Consolidated BRCA1/2 Variant Interpretation by MH BRCA Correlates with Predicted PARP Inhibitor Efficacy Association by MH Guide.
    • Hirotsu Y, Schmidt-Edelkraut U, Nakagomi H, Sakamoto I, Hartenfeller M, Narang R, Soldatos TG, Kaduthanam S, Wang X, Hettich S, Brock S, Jackson DB, Omata M.
    • Int J Mol Sci. 2020 May 29;21(11):E3895. doi: 10.3390/ijms21113895.
    • High-throughput functional evaluation of BRCA2 variants of unknown significance.
    • Ikegami M, Kohsaka S, Ueno T, Momozawa Y, Inoue S, Tamura K, Shimomura A, Hosoya N, Kobayashi H, Tanaka S, Mano H.
    • Nat Commun. 2020 May 22;11(1):2573. doi: 10.1038/s41467-020-16141-8.
    • Spectrum of Germline BRCA1 and BRCA2 Variants Identified in 2351 Ovarian and Breast Cancer Patients Referring to a Reference Cancer Hospital of Rome.
    • Santonocito C, Rizza R, Paris I, Marchis L, Paolillo C, Tiberi G, Scambia G, Capoluongo E.
    • Cancers (Basel). 2020 May 19;12(5):E1286. doi: 10.3390/cancers12051286.
    • Alternative mRNA splicing can attenuate the pathogenicity of presumed loss-of-function variants in BRCA2.
    • Mesman RLS, Calléja FMGR, de la Hoya M, Devilee P, van Asperen CJ, Vrieling H, Vreeswijk MPG.
    • Genet Med. 2020 May 13. doi: 10.1038/s41436-020-0814-5. Epub ahead of print.
    • Functional evaluation of five BRCA2 unclassified variants identified in a Sri Lankan cohort with inherited cancer syndromes using a mouse embryonic stem cell-based assay.
    • Sirisena N, Biswas K, Sullivan T, Stauffer S, Cleveland L, Southon E, Dissanayake VHW, Sharan SK.
    • Breast Cancer Res. 2020 May 11;22(1):43. doi: 10.1186/s13058-020-01272-z.
    • Bypass of premature stop codons and generation of functional BRCA2 by exon skipping.
    • Stauffer S, Biswas K, Sharan SK.
    • J Hum Genet. 2020 May 11. doi: 10.1038/s10038-020-0768-0. Epub ahead of print.
    • Prediction of the functional impact of missense variants in BRCA1 and BRCA2 with BRCA-ML.
    • Hart SN, Polley EC, Shimelis H, Yadav S, Couch FJ.
    • NPJ Breast Cancer. 2020 Apr 29;6(1):13. doi: 10.1038/s41523-020-0159-x.

    Duplicate of:

    • Prediction of the functional impact of missense variants in BRCA1 and BRCA2 with BRCA-ML.
    • Hart SN, Polley EC, Shimelis H, Yadav S, Couch FJ.
    • NPJ Breast Cancer. 2020 Apr 29;6:13. doi: 10.1038/s41523-020-0159-x. eCollection 2020.
    • Tumor sequencing is useful to refine the analysis of germline variants in unexplained high-risk breast cancer families.
    • Van Marcke C, Helaers R, De Leener A, Merhi A, Schoonjans , Ambroise J, Galant C, Delrée P, Rothé F, Bar I, Khoury E, Brouillard P, Canon JL, Vuylsteke P, Machiels JP, Berlière M, Limaye N, Vikkula M, Duhoux FP.
    • Breast Cancer Res. 2020 Apr 15;22(1):36. doi: 10.1186/s13058-020-01273-y.
    • Skipping Nonsense to Maintain Function: The Paradigm of BRCA2 Exon 12.
    • Meulemans L, Mesman RLS, Caputo SM, Krieger S, Guillaud-Bataille M, Caux-Moncoutier V, Léone M, Boutry-Kryza N, Sokolowska J, Révillion F, Delnatte C, Tubeuf H, Soukarieh O, Bonnet-Dorion F, Guibert V, Bronner M, Bourdon V, Lizard S, Vilquin P, Privat M, Drouet A, Grout C, Calléja FMGR, Golmard L, Vrieling H, Stoppa-Lyonnet D, Houdayer C, Frebourg T, Vreeswijk MPG, Martins A, Gaildrat P.
    • Cancer Res. 2020 Apr 1;80(7):1374-1386. doi: 10.1158/0008-5472.CAN-19-2491. Epub 2020 Feb 11.
    • Missense PALB2 germline variant disrupts nuclear localization of PALB2 in a patient with breast cancer.
    • Toh MR, Low CE, Chong ST, Chan SH, Ishak NDB, Courtney E, Kolinjivadi AM Rodrigue A, Masson JY, Ngeow J.
    • Fam Cancer. 2020 Apr;19(2):123-131. doi: 10.1007/s10689-020-00163-8.
    • Case report
    • Criteria of the German Consortium for Hereditary Breast and Ovarian Cancer for the Classification of Germline Sequence Variants in Risk Genes for Hereditary Breast and Ovarian Cancer.
    • Wappenschmidt B, Hauke J, Faust U, Niederacher D, Wiesmüller L, Schmidt G, Groß E, Gehrig A, Sutter C, Ramser J, Rump A, Arnold N, Meindl A.
    • Geburtshilfe Frauenheilkd. 2020 Apr;80(4):410-429. doi: 10.1055/a-1110-0909. Epub 2020 Apr 21.
    • Classification of VUS and unclassified variants in BRCA1 BRCT repeats by molecular dynamics simulation.
    • Sinha S, Wang SM.
    • Comput Struct Biotechnol J. 2020 Mar 21;18:723-736. doi: 10.1016/j.csbj.2020.03.013. eCollection 2020.
    • Consistency of the Tools That Predict the Impact of Single Nucleotide Variants (SNVs) on Gene Functionality: The BRCA1 Gene.
    • Murillo J, Spetale F, Guillaume S, Bulacio P, Garcia Labari I, Cailloux O, Destercke S, Tapia E.
    • Biomolecules. 2020 Mar 20;10(3). pii: E475. doi: 10.3390/biom10030475.
    • Variants of uncertain clinical significance in hereditary breast and ovarian cancer genes: best practices in functional analysis for clinical annotation.
    • Monteiro AN, Bouwman P, Kousholt AN, Eccles DM, Millot GA, Masson JY, Schmidt MK, Sharan SK, Scully R, Wiesmüller L, Couch F, Vreeswijk MPG.
    • J Med Genet. 2020 Mar 9. pii: jmedgenet-2019-106368. doi: 10.1136/jmedgenet-2019-106368. [Epub ahead of print]
    • Review
    • Splicing profile by capture RNA-seq identifies pathogenic germline variants in tumor suppressor genes.
    • Landrith T, Li B, Cass AA, Conner BR, LaDuca H, McKenna DB, Maxwell KN, Domchek S, Morman NA, Heinlen C, Wham D, Koptiuch C, Vagher J, Rivera R, Bunnell A, Patel G, Geurts JL, Depas MM, Gaonkar S, Pirzadeh-Miller S, Krukenberg R, Seidel M, Pilarski R, Farmer M, Pyrtel K, Milliron K, Lee J, Hoodfar E, Nathan D, Ganzak AC, Wu S, Vuong H, Xu D, Arulmoli A, Parra M, Hoang L, Molparia B, Fennessy M, Fox S, Charpentier S, Burdette J, Pesaran T, Profato J, Smith B, Haynes G, Dalton E, Crandall JR, Baxter R, Lu HM, Tippin-Davis B, Elliott A, Chao E, Karam R.
    • NPJ Precis Oncol. 2020 Feb 24;4:4. doi: 10.1038/s41698-020-0109-y. eCollection 2020.
    • Classifying variants of unknown significance in BRCA1/BRCA2 based on family and personal history.
    • Graber C, Goldgar D.
    • Genetics in Medicine. Genepod. 2020 Jan 20.
    • Podcast

    Related:

    Original research:

    Classification of variants of uncertain significance in BRCA1 and BRCA2 using personal and family history of cancer from individuals in a large hereditary cancer multigene panel testing cohort.

    • Systematic misclassification of missense variants in BRCA1 and BRCA2 "coldspots".
    • Dines JN, Shirts BH, Slavin TP, Walsh T, King MC, Fowler DM, Pritchard CC.
    • Genet Med. 2020 Jan 8. doi: 10.1038/s41436-019-0740-6. [Epub ahead of print]
    • Impact of proactive high-throughput functional assay data on BRCA1 variant interpretation in 3684 patients with breast or ovarian cancer.
    • Kim HK, Lee EJ, Lee YJ, Kim J, Kim Y, Kim K, Lee SW, Chang S, Lee YJ, Lee JW, Lee W, Chun S, Son BH, Jung KH, Kim YM, Min WK, Ahn SH.
    • J Hum Genet. 2020 Jan 6. doi: 10.1038/s10038-019-0713-2. [Epub ahead of print]
    • Classification of variants of uncertain significance in BRCA1 and BRCA2 using personal and family history of cancer from individuals in a large hereditary cancer multigene panel testing cohort.
    • Li H, LaDuca H, Pesaran T, Chao EC, Dolinsky JS, Parsons M, Spurdle AB, Polley EC, Shimelis H, Hart SN, Hu C, Couch FJ, Goldgar DE.
    • Genet Med. 2019 Dec 19. doi: 10.1038/s41436-019-0729-1. [Epub ahead of print]

    Related:

    Podcast: Classifying variants of unknown significance in BRCA1/BRCA2 based on family and personal history (Genetics in Medicine Genepod)

    • Ambry Genetics Gains NYS Approval for Paired RNA, DNA Genetic Test.
    • [No author given]
    • GenomeWeb. 2019 Dec 16.

    Related:

    Original research:

    Assessment of Diagnostic Outcomes of RNA Genetic Testing for Hereditary Cancer.

    Press: Ambry Genetics Study Finds RNA Testing Can Clarify Role of Variants in Hereditary Cancer Genes. (GenomeWeb)

    • Characterization of splice-altering mutations in inherited predisposition to cancer.
    • Casadei S, Gulsuner S, Shirts BH, Mandell JB, Kortbawi HM, Norquist BS, Swisher EM, Lee MK, Goldberg Y, O'Connor R, Tan Z, Pritchard CC, King MC, Walsh T.
    • Proc Natl Acad Sci U S A. 2019 Dec 16. pii: 201915608. doi: 10.1073/pnas.1915608116. [Epub ahead of print]

    Related:

    Comments from NSGC Cancer SIG Discussion Forum

    Subject: cBROCA Technology for Detecting Cancer Gene Splicing Variants Published in PNAS

    • Spliceogenic analysis of BRCA1 c.439T>C (rs794727800) variant by High Resolution Melting Analysis.
    • Minucci A, Mazzuccato G, D'Indinosante M, Di Nardo L, Concolino P, De Bonis M, Urbani A, Scambia G, Fagotti A, Capoluongo E.
    • Mol Biol Rep. 2019 Dec 12. doi: 10.1007/s11033-019-05199-3. [Epub ahead of print]
    • Results of multigene panel testing in familial cancer cases without genetic cause demonstrated by single gene testing.
    • Dominguez-Valentin M, Nakken S, Tubeuf H, Vodak D, Ekstrøm PO, Nissen AM, Morak M, Holinski-Feder E, Holth A, Capella G, Davidson B, Evans DG, Martins A, Møller P, Hovig E.
    • Sci Rep. 2019 Dec 6;9(1):18555. doi: 10.1038/s41598-019-54517-z.

    Related:

    Press: Gene Panel Finds Pathogenic Variants Missed by Standard Tests in 5 Percent of Familial Cancer Cases. (GenomeWeb)

    • In silico analysis for determining the deleterious nonsynonymous single nucleotide polymorphisms of BRCA genes.
    • Yadegari F, Majidzadeh K.
    • Mol Biol Res Commun. 2019 Dec;8(4):141-150. doi: 10.22099/mbrc.2019.34198.1420.
    • A dominant RAD51C pathogenic splicing variant predisposes to breast and ovarian cancer in the Newfoundland population due to founder effect.
    • Dawson LM, Smith KN, Werdyani S, Ndikumana R, Penney C, Wiede LL, Smith KL, Pater JA, MacMillan A, Green J, Drover S, Young TL, O'Rielly DD.
    • Mol Genet Genomic Med. 2019 Nov 28:e1070. doi: 10.1002/mgg3.1070. [Epub ahead of print]
    • Functional analysis of genetic variants in the high-risk breast cancer susceptibility gene PALB2.
    • Boonen RACM, Rodrigue A, Stoepker C, Wiegant WW, Vroling B, Sharma M, Rother MB, Celosse N, Vreeswijk MPG, Couch F, Simard J, Devilee P, Masson JY, van Attikum H.
    • Nat Commun. 2019 Nov 22;10(1):5296. doi: 10.1038/s41467-019-13194-2.
    • From a variant of unknown significance to pathogenic: Reclassification of a large novel duplication in BRCA2 by high-throughput sequencing.
    • van Luttikhuizen JL, Bublitz J, Schubert S, Schmidt G, Hofmann W, Morlot S, Buurman R, Auber B, Schlegelberger B, Steinemann D.
    • Mol Genet Genomic Med. 2019 Nov 13:e1045. doi: 10.1002/mgg3.1045. [Epub ahead of print]
    • Determination of Pathogenicity of Breast Cancer 1 Gene Variants using the American College of Medical Genetics and Genomics and the Association for Molecular Pathology Guidelines.
    • Brown A, Zamanpoor M, Love DR, Prosser DO.
    • Sultan Qaboos Univ Med J. 2019 Nov;19(4):e324-e334. doi: 10.18295/squmj.2019.19.04.008. Epub 2019 Dec 22.
    • Comparison of Somatic and Germline Variant Interpretation in Hereditary Cancer Genes.
    • Moody EW, Vagher J, Espinel W, Goldgar D, Hagerty KJ, Gammon A.
    • JCO Precis Oncol. 2019 Dec [2019 Oct 30];3:1-8. doi: 10.1200/PO.19.00144.
    • Functional characterization of 84 PALB2 variants of uncertain significance.
    • Wiltshire T, Ducy M, Foo TK, Hu C, Lee KY, Belur Nagaraj A, Rodrigue A, Gomes TT, Simard J, Monteiro ANA, Xia B, Carvalho MA, Masson JY, Couch FJ.
    • Genet Med. 2019 Oct 21. doi: 10.1038/s41436-019-0682-z. [Epub ahead of print]
    • A global functional analysis of missense mutations reveals two major hotspots in the PALB2 tumor suppressor.
    • Rodrigue A, Margaillan G, Torres Gomes T, Coulombe Y, Montalban G, da Costa E Silva Carvalho S, Milano L, Ducy M, De-Gregoriis G, Dellaire G, Araújo da Silva W Jr, Monteiro AN, Carvalho MA, Simard J, Masson JY.
    • Nucleic Acids Res. 2019 Oct 5. pii: gkz780. doi: 10.1093/nar/gkz780. [Epub ahead of print]
    • Adding RNA-Seq, Ambry Genetics Expects to Reduce VUS Results in Hereditary Cancer Tests.
    • [No author given]
    • GenomeWeb. 2019 Oct 4.
    • News
    • Assessment of Diagnostic Outcomes of RNA Genetic Testing for Hereditary Cancer.
    • Karam R, Conner B, LaDuca H, McGoldrick K, Krempely K, Richardson ME, Zimmermann H, Gutierrez S, Reineke P, Hoang L, Allen K, Yussuf A, Farber-Katz S, Rana HQ, Culver S, Lee J, Nashed S, Toppmeyer D, Collins D, Haynes G, Pesaran T, Dolinsky JS, Tippin Davis B, Elliott A, Chao E.
    • JAMA Netw Open. 2019 Oct 2;2(10):e1913900. doi: 10.1001/jamanetworkopen.2019.13900.

    Related:

    Press: Ambry Genetics Study Finds RNA Testing Can Clarify Role of Variants in Hereditary Cancer Genes. (GenomeWeb)

    Press: Ambry Genetics Gains NYS Approval for Paired RNA, DNA Genetic Test. (GenomeWeb)

    • A Functional Analysis of the Unclassified Pro2767Ser BRCA2 Variant Reveals Its Potential Pathogenicity that Acts by Hampering DNA Binding and Homology-Mediated DNA Repair.
    • Esposito MV, Minopoli G, Esposito L, D'Argenio V, Di Maggio F, Sasso E, D'Aiuto M, Zambrano N, Salvatore F.
    • Cancers (Basel). 2019 Sep 28;11(10). pii: E1454. doi: 10.3390/cancers11101454.
    • Novel Genetic Markers for Early Detection of Elevated Breast Cancer Risk in Women.
    • Wu B, Peng Y, Eggert J, Alexov E.
    • Int J Mol Sci. 2019 Sep 28;20(19). pii: E4828. doi: 10.3390/ijms20194828.
    • Functional investigation of the BRCA1 Val1714Gly and Asp1733Gly variants by computational tools and yeast transcription activation assay.
    • Yadegari F, Farahmand L, Esmaeili R, Samadi T, Majidzadeh K.
    • Mol Biol Res Commun. 2019 Sep;8(3):113-118. doi: 10.22099/mbrc.2019.33971.1414.
    • A CRISPR-based base-editing screen for the functional assessment of BRCA1 variants.
    • Kweon J, Jang AH, Shin HR, See JE, Lee W, Lee JW, Chang S, Kim K, Kim Y.
    • Oncogene. 2019 Aug 29. doi: 10.1038/s41388-019-0968-2. [Epub ahead of print]
    • A novel BRCA1 germline mutation promotes triple-negative breast cancer cells progression and enhances sensitivity to DNA damage agents.
    • Xu K, Shi Y, Wang X, Chen Y, Tang L, Guan X.
    • Cancer Genet. 2019 Aug 23;239:26-32. doi: 10.1016/j.cancergen.2019.08.004. [Epub ahead of print]
    • Functional analysis of clinical BARD1 germline variants.
    • Toh MR, Chong ST, Chan SH, Low CE, Ishak NDB, Lim JQ, Courtney E, Ngeow J.
    • Cold Spring Harb Mol Case Stud. 2019 Aug 1;5(4). pii: a004093. doi: 10.1101/mcs.a004093. Print 2019 Aug.
    • Incorporation of semi-quantitative analysis of splicing alterations for the clinical interpretation of variants in BRCA1 and BRCA2 genes.
    • Montalban G, Bonache S, Moles-Fernández A, Gadea N, Tenés A, Torres-Esquius S, Carrasco E, Balmaña J, Diez O, Gutiérrez-Enríquez S.
    • Hum Mutat. 2019 Jul 25. doi: 10.1002/humu.23882. [Epub ahead of print]
    • Targeted RNA-seq successfully identifies normal and pathogenic splicing events in breast/ovarian cancer susceptibility and Lynch syndrome genes.
    • Brandão RD, Mensaert K, López-Perolio I, Tserpelis D, Xenakis M, Lattimore V, Walker LC, Kvist A, Vega A, Gutiérrez-Enríquez S, Díez O; KConFaB Investigators, de la Hoya M, Spurdle AB, De Meyer T, Blok MJ.
    • Int J Cancer. 2019 Jul 15;145(2):401-414. doi: 10.1002/ijc.32114. Epub 2019 Feb 7.
    • Assessment of blind predictions of the clinical significance of BRCA1 and BRCA2 variants.
    • Cline MS, Babbi G, Bonache S, Cao Y, Casadio R, de la Cruz X, Díez O, Gutiérrez-Enríquez S, Katsonis P, Lai C, Lichtarge O, Martelli PL, Mishne G, Moles-Fernández A, Montalban G, Mooney SD, O'Conner R, Ootes L, Özkan S, Padilla N, Pagel KA, Pejaver V, Radivojac P, Riera C, Savojardo C, Shen Y, Sun Y, Topper S, Parsons MT, Spurdle AB, Goldgar DE; ENIGMA Consortium.
    • Hum Mutat. 2019 Jul 11. doi: 10.1002/humu.23861. [Epub ahead of print]
    • Functional coding and non-coding variants in human BRCA1 gene and their use in genetic screening.
    • Tuncel G, Ergören MÇ.
    • Med Oncol. 2019 Jul 3;36(8):71. doi: 10.1007/s12032-019-1294-9.
    • Review
    • Assessing the performance of in-silico methods for predicting the pathogenicity of variants in the gene CHEK2, among Hispanic females with breast cancer.
    • Voskanian A, Katsonis P, Lichtarge O, Pejaver V, Radivojac P, Mooney SD, Capriotti E, Bromberg Y, Wang Y, Miller M, Martelli PL, Savojardo C, Babbi G, Casadio R, Cao Y, Sun Y, Shen Y, Garg A, Pal D, Yu Y, Huff CD, Tavtigian SV, Young E, Neuhausen SL, Ziv E, Pal LR, Andreoletti G, Brenner S, Kann M.
    • Hum Mutat. 2019 Jun 26. doi: 10.1002/humu.23849. [Epub ahead of print]
    • Discovery of a pathogenic variant rs139379666 (p. P2974L) in ATM for breast cancer risk in Chinese populations.
    • Guo X, Lin W, Bai M, Li H, Wen W, Zeng C, Chen Z, He J, Chen J, Cai Q, Long J, Jia WH, Shu XO, Zheng W.
    • Cancer Epidemiol Biomarkers Prev. 2019 Jun 3. pii: cebp.1294.2018. doi: 10.1158/1055-9965.EPI-18-1294. [Epub ahead of print]
    • [Germline CHEK2 Gene Mutations in Hereditary Breast Cancer Predisposition - Mutation Types and their Biological and Clinical Relevance.]
    • Kleiblová P, Stolařová L, Křížová K, Lhota F, Hojný J, Zemánková P, Havránek O, Vočka M, Černá M, Lhotová K, Borecká M, Janatová M, Soukupová J, Ševčík J, Zimovjanová M, Kotlas J, Panczak A, Veselá K, Červenková J, Schneiderová M, Burócziová M, Burdová K, Stránecký V, Foretová L, Macháčková E, Tavandzis S, Kmoch S, Macůrek L, Kleibl Z.
    • Klin Onkol. 2019 Summer;32(Supplementum2):36-50. doi: 10.14735/amko2019S36.
    • Hereditary Cancer Syndromes-A Primer on Diagnosis and Management: Part 1: Breast-Ovarian Cancer Syndromes.
    • Samadder NJ, Giridhar KV, Baffy N, Riegert-Johnson D, Couch FJ.
    • Mayo Clin Proc. 2019 Jun;94(6):1084-1098. doi: 10.1016/j.mayocp.2019.02.017.
    • Predicting Pathogenicity of Missense Variants with Weakly Supervised Regression.
    • Cao Y, Sun Y, Karimi M, Chen H, Moronfoye O, Shen Y.
    • Hum Mutat. 2019 May 30. doi: 10.1002/humu.23826. [Epub ahead of print]
    • Minigene Splicing Assays Identify 12 Spliceogenic Variants of BRCA2 Exons 14 and 15.
    • Fraile-Bethencourt E, Valenzuela-Palomo A, Díez-Gómez B, Caloca MJ, Gómez-Barrero S, Velasco EA.
    • Front Genet. 2019 May 28;10:503. doi: 10.3389/fgene.2019.00503. eCollection 2019.
    • Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification.
    • Parsons MT, Tudini E, Li H, Hahnen E, Wappenschmidt B, Feliubadaló L, Aalfs CM, Agata S, Aittomäki K, Alducci E, Alonso-Cerezo MC, Arnold N, Auber B, Austin R, Azzollini J, Balmaña J, Barbieri E, Bartram CR, Blanco A, Blümcke B, Bonache S, Bonanni B, Borg Å, Bortesi B, Brunet J, Bruzzone C, Bucksch K, Cagnoli G, Caldés T, Caliebe A, Caligo MA, Calvello M, Capone GL, Caputo SM, Carnevali I, Carrasco E, Caux-Moncoutier V, Cavalli P, Cini G, Clarke EM, Concolino P, Cops EJ, Cortesi L, Couch FJ, Darder E, de la Hoya M, Dean M, Debatin I, Del Valle J, Delnatte C, Derive N, Diez O, Ditsch N, Domchek SM, Dutrannoy V, Eccles DM, Ehrencrona H, Enders U, Evans DG, Faust U, Felbor U, Feroce I, Fine M, Galvao HCR, Gambino G, Gehrig A, Gensini F, Gerdes AM, Germani A, Giesecke J, Gismondi V, Gómez C, Gómez Garcia EB, González S, Grau E, Grill S, Gross E, Guerrieri-Gonzaga A, Guillaud-Bataille M, Gutiérrez-Enríquez S, Haaf T, Hackmann K, Hansen TVO, Harris M, Hauke J, Heinrich T, Hellebrand H, Herold KN, Honisch E, Horvath J, Houdayer C, Hübbel V, Iglesias S, Izquierdo A, James PA, Janssen LAM, Jeschke U, Kaulfuß S, Keupp K, Kiechle M, Kölbl A, Krieger S, Kruse TA, Kvist A, Lalloo F, Larsen M, Lattimore VL, Lautrup C, Ledig S, Leinert E, Lewis AL, Lim J, Loeffler M, López-Fernández A, Lucci-Cordisco E, Maass N, Manoukian S, Marabelli M, Matricardi L, Meindl A, Michelli RD, Moghadasi S, Moles-Fernández A, Montagna M, Montalban G, Monteiro AN, Montes E, Mori L, Moserle L, Müller CR, Mundhenke C, Naldi N, Nathanson KL, Navarro M, Nevanlinna H, Nichols CB, Niederacher D, Nielsen HR, Ong KR, Pachter N, Palmero EI, Papi L, Pedersen IS, Peissel B, Pérez-Segura P, Pfeifer K, Pineda M, Pohl-Rescigno E, Poplawski NK, Porfirio B, Quante AS, Ramser J, Reis RM, Revillion F, Rhiem K, Riboli B, Ritter J, Rivera D, Rofes P, Rump A, Salinas M, Sánchez de Abajo AM, Schmidt G, Schoenwiese U, Seggewiß J, Solanes A, Steinemann D, Stiller M, Stoppa-Lyonnet D, Sullivan KJ, Susman R, Sutter C, Tavtigian SV, Teo SH, Teulé A, Thomassen M, Tibiletti MG, Tognazzo S, Toland AE, Tornero E, Törngren T, Torres-Esquius S, Toss A, Trainer AH, van Asperen CJ, van Mackelenbergh MT, Varesco L, Vargas-Parra G, Varon R, Vega A, Velasco Á, Vesper AS, Viel A, Vreeswijk MPG, Wagner SA, Waha A, Walker LC, Walters RJ, Wang-Gohrke S, Weber BHF, Weichert W, Wieland K, Wiesmüller L, Witzel I, Wöckel A, Woodward ER, Zachariae S, Zampiga V, Zeder-Göß C; KConFab Investigators, Lázaro C, De Nicolo A, Radice P, Engel C, Schmutzler RK, Goldgar DE, Spurdle AB.
    • Hum Mutat. 2019 May 27. doi: 10.1002/humu.23818. [Epub ahead of print]
    • Diagnostic mRNA splicing assay for variants in BRCA1 and BRCA2 identified two novel pathogenic splicing aberrations.
    • Wangensteen T, Felde CN, Ahmed D, Mæhle L, Ariansen SL.
    • Hered Cancer Clin Pract. 2019 May 22;17:14. doi: 10.1186/s13053-019-0113-9. eCollection 2019.
    • BRCA1- and BRCA2-specific in silico tools for variant interpretation in the CAGI 5 ENIGMA challenge.
    • Padilla N, Moles-Fernández A, Riera C, Montalban G, Özkan S, Ootes L, Bonache S, Díez O, Gutiérrez-Enríquez S, de la Cruz X.
    • Hum Mutat. 2019 May 21. doi: 10.1002/humu.23802. [Epub ahead of print]
    • Exploring the use of molecular dynamics in assessing protein variants for phenotypic alterations.
    • Garg A, Pal D.
    • Hum Mutat. 2019 May 20. doi: 10.1002/humu.23800. [Epub ahead of print]
    • Whole-genome sequencing reveals clinically relevant insights into the aetiology of familial breast cancers.
    • Nones K, Johnson J, Newell F, Patch AM, Thorne H, Kazakoff SH, de Luca XM, Parsons MT, Ferguson K, Reid L, Reed AEM, Srihari S, Lakis V, Davidson AL, Mukhopadhyay P, Holmes O, Xu Q, Wood S, Leonard C; Kathleen Cuningham Foundation Consortium for Research into Familial Aspects of Breast Cancer (kConFab); Australian Breast Cancer Tissue Bank (ABCTB); Brisbane Breast Bank (BBB), Beesley J, Harris J, Barnes D, Degasperi A, Ragan MA, Spurdle AB, Khanna KK, Lakhani SR, Pearson JV, Nik-Zainal S, Chenevix-Trench G, Waddell N, Simpson PT.
    • Ann Oncol. 2019 May 15. pii: mdz132. doi: 10.1093/annonc/mdz132. [Epub ahead of print]

    Related:

    Editorial:

    Journey's End: the quest for BRCA-like hereditary breast cancer genes is nearly over.

    • Identification of deleterious germline CHEK2 mutations and their association with breast and ovarian cancer.
    • Kleiblova P, Stolarova L, Krizova K, Lhota F, Hojny J, Zemankova P, Havranek O, Vocka M, Cerna M, Lhotova K, Borecka M, Janatova M, Soukupova J, Sevcik J, Zimovjanova M, Kotlas J, Panczak A, Vesela K, Cervenkova J, Schneiderova M, Burocziova M, Burdova K, Stranecky V, Foretova L, Machackova E, Tavandzis S, Kmoch S, Macurek L, Kleibl Z.
    • Int J Cancer. 2019 May 3. doi: 10.1002/ijc.32385. [Epub ahead of print]
    • Functional characterization of CHEK2 variants in a Saccharomyces cerevisiae system.
    • Delimitsou A, Fostira F, Kalfakakou D, Apostolou P, Konstantopoulou I, Kroupis C, Papavassiliou AG, Kleibl Z, Stratikos E, Voutsinas GE, Yannoukakos D.
    • Hum Mutat. 2019 May;40(5):631-648. doi: 10.1002/humu.23728. Epub 2019 Mar 9.
    • A reference system for BRCA mutation detection based on next-generation sequencing in the Chinese population.
    • Qu S, Chen Q, Yi Y, Shao K, Zhang W, Wang Y, Bai J, Li X, Liu Z, Wang X, Jing R, Guan Y, Yi X, Yan M, Cao B, Chen F, Zhu S, Yang X, Wu Y, Huang J.
    • J Mol Diagn. 2019 Apr 23. pii: S1525-1578(18)30284-8. doi: 10.1016/j.jmoldx.2019.03.003. [Epub ahead of print]
    • Germline Missense Variants in BRCA1: New Trends and Challenges for Clinical Annotation.
    • Golubeva VA, Nepomuceno TC, Monteiro ANA.
    • Cancers (Basel). 2019 Apr 12;11(4). pii: E522. doi: 10.3390/cancers11040522.
    • Impact of amino acid substitutions at secondary structures in the BRCT domains of the tumor suppressor BRCA1: Implications for clinical annotation.
    • Fernandes VC, Golubeva VA, Di Pietro G, Shields C, Amankwah K, Nepomuceno TC, de Gregoriis G, Abreu RBV, Harro C, Gomes TT, Silva RF, Suarez-Kurtz G, Couch FJ, Iversen ES, Monteiro ANA, Carvalho MA.
    • J Biol Chem. 2019 Apr 12;294(15):5980-5992. doi: 10.1074/jbc.RA118.005274. Epub 2019 Feb 14.
    • Variant classification changes over time in BRCA1 and BRCA2.
    • Mighton C, Charames GS, Wang M, Zakoor KR, Wong A, Shickh S, Watkins N, Lebo MS, Bombard Y, Lerner-Ellis J.
    • Genet Med. 2019 Apr 11. doi: 10.1038/s41436-019-0493-2. [Epub ahead of print]
    • Quick Uptakes: Taking the Uncertainty Out of Interpreting BRCA Variants.
    • Voelker R.
    • JAMA. 2019 Apr 9;321(14):1340-1341. doi: 10.1001/jama.2019.0967.

    Related:

    BRCA Challenge: BRCA Exchange as a global resource for variants in BRCA1 and BRCA2.

    • Data-adaptive multi-locus association testing in subjects with arbitrary genealogical relationships.
    • Gong G, Wang W, Hsieh CL, Van Den Berg DJ, Haiman C, Oakley-Girvan I, Whittemore AS.
    • Stat Appl Genet Mol Biol. 2019 Apr 8. pii: /j/sagmb.ahead-of-print/sagmb-2018-0030/sagmb-2018-0030.xml. doi: 10.1515/sagmb-2018-0030. [Epub ahead of print]
    • Ambry Researchers Report Consequences of RNA-Based Variant Reclassification at ACMG.
    • Anderson A.
    • GenomeWeb. Technology. Sequencing. 2019 Apr 5.
    • Alternative transcript imbalance underlying breast cancer susceptibility in a family carrying PALB2 c.3201+5G>T.
    • Duran-Lozano L, Montalban G, Bonache S, Moles-Fernández A, Tenés A, Castroviejo-Bermejo M, Carrasco E, López-Fernández A, Torres-Esquius S, Gadea N, Stjepanovic N, Balmaña J, Gutiérrez-Enríquez S, Diez O.
    • Breast Cancer Res Treat. 2019 Apr;174(2):543-550. doi: 10.1007/s10549-018-05094-8. Epub 2018 Dec 14.
    • Case report
    • Functional analysis of BARD1 missense variants in homology-directed repair and damage sensitivity.
    • Adamovich AI, Banerjee T, Wingo M, Duncan K, Ning J, Martins Rodrigues F, Huang KL, Lee C, Chen F, Ding L, Parvin JD.
    • PLoS Genet. 2019 Mar 29;15(3):e1008049. doi: 10.1371/journal.pgen.1008049. eCollection 2019 Mar.
    • Alternative splicing and ACMG-AMP-2015-based classification of PALB2 genetic variants: an ENIGMA report.
    • Lopez-Perolio I, Leman R, Behar R, Lattimore V, Pearson JF, Castéra L, Martins A, Vaur D, Goardon N, Davy G, Garre P, García-Barberán V, Llovet P, Pérez-Segura P, Díaz-Rubio E, Caldés T, Hruska KS, Hsuan V, Wu S, Pesaran T, Karam R, Vallon-Christersson J, Borg A, Investigators K, Valenzuela-Palomo A, Velasco EA, Southey M, Vreeswijk MPG, Devilee P, Kvist A, Spurdle AB, Walker LC, Krieger S, de la Hoya M.
    • J Med Genet. 2019 Mar 19. pii: jmedgenet-2018-105834. doi: 10.1136/jmedgenet-2018-105834. [Epub ahead of print]
    • Mis-splicing in breast cancer: identification of pathogenic BRCA2 variants by systematic minigene assays.
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    • J Pathol. 2019 Mar 18. doi: 10.1002/path.5268. [Epub ahead of print]
    • Usefulness and Limitations of Comprehensive Characterization of mRNA Splicing Profiles in the Definition of the Clinical Relevance of BRCA1/2 Variants of Uncertain Significance.
    • Gelli E, Colombo M, Pinto AM, De Vecchi G, Foglia C, Amitrano S, Morbidoni V, Imperatore V, Manoukian S, Baldassarri M, Lo Rizzo C, Catania L, Frullanti E, Tagliafico E, Cortesi L, Spaggiari F, Mencarelli MA, Trevisson E, Radice P, Renieri A, Ariani F.
    • Cancers (Basel). 2019 Mar 1;11(3). pii: E295. doi: 10.3390/cancers11030295.
    • DNA breakpoint assay reveals a majority of gross duplications occur in tandem reducing VUS classifications in breast cancer predisposition genes.
    • Richardson ME, Chong H, Mu W, Conner BR, Hsuan V, Willett S, Lam S, Tsai P, Pesaran T, Chamberlin AC, Park MS, Gray P, Karam R, Elliott A.
    • Genet Med. 2019 Mar;21(3):683-693. doi: 10.1038/s41436-018-0092-7. Epub 2018 Jul 28.
    • BRCA1/2 Variant Data-Sharing Practices.
    • Bollinger JM, Sanka A, Dolman L, Liao RG, Cook-Deegan R.
    • J Law Med Ethics. 2019 Mar;47(1):88-96. doi: 10.1177/1073110519840487.
    • Toward automation of germline variant curation in clinical cancer genetics.
    • Ravichandran V, Shameer Z, Kemel Y, Walsh M, Cadoo K, Lipkin S, Mandelker D, Zhang L, Stadler Z, Robson M, Offit K, Vijai J.
    • Genet Med. 2019 Feb 21. doi: 10.1038/s41436-019-0463-8. [Epub ahead of print]
    • Integrative data fusion for comprehensive assessment of a novel CHEK2 variant using combined genomics, imaging, and functional-structural assessments via protein informatics.
    • Hines SL, Mohammad AN, Jackson J, Macklin S, Caulfield TR.
    • Mol Omics. 2019 Feb 11;15(1):59-66. doi: 10.1039/c8mo00137e.
    • Quantifying BRCA1 and BRCA2 mRNA Isoform Expression Levels in Single Cells.
    • Lattimore VL, Pearson JF, Morley-Bunker AE, Investigators K, Spurdle AB, Robinson BA, Currie MJ, Walker LC.
    • Int J Mol Sci. 2019 Feb 6;20(3). pii: E693. doi: 10.3390/ijms20030693.
    • The functional impact of variants of uncertain significance in BRCA2.
    • Mesman RLS, Calléja FMGR, Hendriks G, Morolli B, Misovic B, Devilee P, van Asperen CJ, Vrieling H, Vreeswijk MPG.
    • Genet Med. 2019 Feb;21(2):293-302. doi: 10.1038/s41436-018-0052-2. Epub 2018 Jul 10.
    • GFP-Fragment Reassembly Screens for the Functional Characterization of Variants of Uncertain Significance in Protein Interaction Domains of the BRCA1 and BRCA2 Genes.
    • Caleca L, Colombo M, van Overeem Hansen T, Lázaro C, Manoukian S, Parsons MT, Spurdle AB, Radice P.
    • Cancers (Basel). 2019 Jan 28;11(2). pii: E151. doi: 10.3390/cancers11020151.
    • The effects of genomic germline variant reclassification on clinical cancer care.
    • Slavin TP, Manjarrez S, Pritchard CC, Gray S, Weitzel JN.
    • Oncotarget. 2019 Jan 11;10(4):417-423. doi: 10.18632/oncotarget.26501. eCollection 2019 Jan 11.
    • Additional molecular and clinical evidence open the way to definitive IARC classification of the BRCA1 c.5332G > A (p.Asp1778Asn) variant.
    • Minucci A, Lalle M, De Leo R, Mazzuccato G, Scambia G, Urbani A, Fagotti A, Concolino P, Capoluongo E.
    • Clin Biochem. 2019 Jan;63:54-58. doi: 10.1016/j.clinbiochem.2018.10.004. Epub 2018 Oct 10.
    • Comprehensive annotation of BRCA1 and BRCA2 missense variants by functionally validated sequence-based computational prediction models.
    • Hart SN, Hoskin T, Shimelis H, Moore RM, Feng B, Thomas A, Lindor NM, Polley EC, Goldgar DE, Iversen E, Monteiro ANA, Suman VJ, Couch FJ.
    • Genet Med. 2019 Jan;21(1):71-80. doi: 10.1038/s41436-018-0018-4. Epub 2018 Jun 8.
    • Combining Homologous Recombination and Phosphopeptide-binding Data to Predict the Impact of BRCA1 BRCT Variants on Cancer Risk.
    • Petitalot A, Dardillac E, Jacquet E, Nhiri N, Guirouilh-Barbat J, Julien P, Bouazzaoui I, Bonte D, Feunteun J, Schnell JA, Lafitte P, Aude JC, Noguès C, Rouleau E, Lidereau R, Lopez BS, Zinn-Justin S, Caputo SM; UNICANCER Genetic Group BRCA network.
    • Mol Cancer Res. 2019 Jan;17(1):54-69. doi: 10.1158/1541-7786.MCR-17-0357. Epub 2018 Sep 26.
    • Functional evaluation of variants of unknown significance in the BRCA2 gene identified in genetic testing.
    • Heczkova M, Machackova E, Macinga P, Gallmeier E, Cahova M, Spicak J, Jirsa M, Foretova L, Hucl T.
    • Cancer Biol Ther. 2019;20(5):633-641. doi: 10.1080/15384047.2018.1550566. Epub 2019 Jan 13.
    • BRCA Challenge: BRCA Exchange as a global resource for variants in BRCA1 and BRCA2.
    • Cline MS, Liao RG, Parsons MT, Paten B, Alquaddoomi F, Antoniou A, Baxter S, Brody L, Cook-Deegan R, Coffin A, Couch FJ, Craft B, Currie R, Dlott CC, Dolman L, den Dunnen JT, Dyke SOM, Domchek SM, Easton D, Fischmann Z, Foulkes WD, Garber J, Goldgar D, Goldman MJ, Goodhand P, Harrison S, Haussler D, Kato K, Knoppers B, Markello C, Nussbaum R, Offit K, Plon SE, Rashbass J, Rehm HL, Robson M, Rubinstein WS, Stoppa-Lyonnet D, Tavtigian S, Thorogood A, Zhang C, Zimmermann M; BRCA Challenge Authors, Burn J, Chanock S, Rätsch G, Spurdle AB.
    • PLoS Genet. 2018 Dec 26;14(12):e1007752. doi: 10.1371/journal.pgen.1007752. eCollection 2018 Dec.

    Related:

    Research news:

    Quick Uptakes: Taking the Uncertainty Out of Interpreting BRCA Variants.

    • BRCA1 and BRCA2 5' noncoding region variants identified in breast cancer patients alter promoter activity and protein binding.
    • Burke LJ, Sevcik J, Gambino G, Tudini E, Mucaki EJ, Shirley BC, Whiley P, Parsons MT, De Leeneer K, Gutiérrez-Enríquez S, Santamariña M, Caputo SM, Santana Dos Santos E, Soukupova J, Janatova M, Zemankova P, Lhotova K, Stolarova L, Borecka M, Moles-Fernández A, Manoukian S, Bonanni B; ENIGMA Consortium, Edwards SL, Blok MJ, van Overeem Hansen T, Rossing M, Diez O, Vega A, Claes KBM, Goldgar DE, Rouleau E, Radice P, Peterlongo P, Rogan PK, Caligo M, Spurdle AB, Brown MA.
    • Hum Mutat. 2018 Dec;39(12):2025-2039. doi: 10.1002/humu.23652. Epub 2018 Sep 24.
    • Reclassification of BRCA1 and BRCA2 variants of uncertain significance: a multifactorial analysis of multicentre prospective cohort.
    • Lee JS, Oh S, Park SK, Lee MH, Lee JW, Kim SW, Son BH, Noh DY, Lee JE, Park HL, Kim MJ, Cho SI, Lee YK, Park SS, Seong MW.
    • J Med Genet. 2018 Dec;55(12):794-802. doi: 10.1136/jmedgenet-2018-105565. Epub 2018 Nov 10.
    • Big Data Sharing: A Crucial Democratic Issue for Genomic Medicine.
    • Derbez B.
    • Front Public Health. 2018 Nov 28;6:334. doi: 10.3389/fpubh.2018.00334. eCollection 2018.
    • Screening of BRCA1/2 deep intronic regions by targeted gene sequencing identifies the first germline BRCA1 variant causing pseudoexon activation in a patient with breast/ovarian cancer.
    • Montalban G, Bonache S, Moles-Fernández A, Gisbert-Beamud A, Tenés A, Bach V, Carrasco E, López-Fernández A, Stjepanovic N, Balmaña J, Diez O, Gutiérrez-Enríquez S.
    • J Med Genet. 2018 Nov 24. pii: jmedgenet-2018-105606. doi: 10.1136/jmedgenet-2018-105606. [Epub ahead of print]
    • Case report
    • Trans-activation-based risk assessment of BRCA1 BRCT variants with unknown clinical significance.
    • Langerud J, Jarhelle E, Van Ghelue M, Ariansen SL, Iversen N.
    • Hum Genomics. 2018 Nov 20;12(1):51. doi: 10.1186/s40246-018-0183-1.
    • Non-Coding Variants in BRCA1 and BRCA2 Genes: Potential Impact on Breast and Ovarian Cancer Predisposition.
    • Santana Dos Santos E, Lallemand F, Burke L, Stoppa-Lyonnet D, Brown M, Caputo SM, Rouleau E.
    • Cancers (Basel). 2018 Nov 16;10(11). pii: E453. doi: 10.3390/cancers10110453.
    • Substantial evidence for the clinical significance of missense variant BRCA1 c.5309G>T p.(Gly1770Val).
    • Tudini E, Moghadasi S, Parsons MT, van der Kolk L, van den Ouweland AMW, Niederacher D, Feliubadaló L, Wappenschmidt B, Spurdle AB, Lazaro C.
    • Breast Cancer Res Treat. 2018 Nov;172(2):497-503. doi: 10.1007/s10549-018-4903-y. Epub 2018 Aug 13.
    • Specifications of the ACMG/AMP variant curation guidelines for the analysis of germline CDH1 sequence variants.
    • Lee K, Krempely K, Roberts ME, Anderson MJ, Carneiro F, Chao E, Dixon K, Figueiredo J, Ghosh R, Huntsman D, Kaurah P, Kesserwan C, Landrith T, Li S, Mensenkamp AR, Oliveira C, Pardo C, Pesaran T, Richardson M, Slavin TP, Spurdle AB, Trapp M, Witkowski L, Yi CS, Zhang L, Plon SE, Schrader KA, Karam R.
    • Hum Mutat. 2018 Nov;39(11):1553-1568. doi: 10.1002/humu.23650.
    • Two Missense Variants Detected in Breast Cancer Probands Preventing BRCA2-PALB2 Protein Interaction.
    • Caleca L, Catucci I, Figlioli G, De Cecco L, Pesaran T, Ward M, Volorio S, Falanga A, Marchetti M, Iascone M, Tondini C, Zambelli A, Azzollini J, Manoukian S, Radice P, Peterlongo P.
    • Front Oncol. 2018 Oct 25;8:480. doi: 10.3389/fonc.2018.00480. eCollection 2018.
    • A Multiplex Homology-Directed DNA Repair Assay Reveals the Impact of More Than 1,000 BRCA1 Missense Substitution Variants on Protein Function.
    • Starita LM, Islam MM, Banerjee T, Adamovich AI, Gullingsrud J, Fields S, Shendure J, Parvin JD.
    • Am J Hum Genet. 2018 Oct 4;103(4):498-508. doi: 10.1016/j.ajhg.2018.07.016. Epub 2018 Sep 12.
    • Accurate classification of BRCA1 variants with saturation genome editing.
    • Findlay GM, Daza RM, Martin B, Zhang MD, Leith AP, Gasperini M, Janizek JD, Huang X, Starita LM, Shendure J4.
    • Nature. 2018 Oct;562(7726):217-222. doi: 10.1038/s41586-018-0461-z. Epub 2018 Sep 12.

    Related:

    Research News: Gene editing reveals the effect of thousands of variants in a key cancer gene (Nature)

    Research News: A CRISPR Approach for Accurately Classifying BRCA1 Variants. (Medscape Oncology)

    Research News: A new method for determining whether genetic variants in BRCA1 increase cancer risk. (FORCE XRAYS)

    Research news:

    Technique Pinpoints Oncogenic BRCA1 Mutations.

    • Exome-wide analysis of bi-allelic alterations identifies a Lynch phenotype in The Cancer Genome Atlas.
    • Buckley AR, Ideker T, Carter H, Harismendy O, Schork NJ.
    • Genome Med. 2018 Sep 14;10(1):69. doi: 10.1186/s13073-018-0579-5.
    • Dealing With BRCA1/2 Unclassified Variants in a Cancer Genetics Clinic: Does Cosegregation Analysis Help?
    • Zuntini R, Ferrari S, Bonora E, Buscherini F, Bertonazzi B, Grippa M, Godino L, Miccoli S, Turchetti D.
    • Front Genet. 2018 Sep 11;9:378. doi: 10.3389/fgene.2018.00378. eCollection 2018.
    • Novel diagnostic tool for prediction of variant spliceogenicity derived from a set of 395 combined in silico/in vitro studies: an international collaborative effort.
    • Leman R, Gaildrat P, Gac GL, Ka C, Fichou Y, Audrezet MP, Caux-Moncoutier V, Caputo SM, Boutry-Kryza N, Léone M8, Mazoyer S, Bonnet-Dorion F, Sevenet N, Guillaud-Bataille M, Rouleau E, Bressac-de Paillerets B, Wappenschmidt B, Rossing M, Muller D, Bourdon V, Revillon F, Parsons MT, Rousselin A, Davy G, Castelain G, Castéra L, Sokolowska J, Coulet F, Delnatte C, Férec C, Spurdle AB, Martins A, Krieger S, Houdayer C.
    • Nucleic Acids Res. 2018 Sep 6;46(15):7913-7923. doi: 10.1093/nar/gky372.
    • Computational Tools for Splicing Defect Prediction in Breast/Ovarian Cancer Genes: How Efficient Are They at Predicting RNA Alterations?
    • Moles-Fernández A, Duran-Lozano L, Montalban G, Bonache S, López-Perolio I, Menéndez M, Santamariña M, Behar R, Blanco A, Carrasco E, López-Fernández A, Stjepanovic N, Balmaña J, Capellá G, Pineda M, Vega A, Lázaro C, de la Hoya M, Diez O, Gutiérrez-Enríquez S.
    • Front Genet. 2018 Sep 5;9:366. doi: 10.3389/fgene.2018.00366. eCollection 2018.
    • Characterization of spliceogenic variants located in regions linked to high levels of alternative splicing: BRCA2 c.7976+5G > T as a case study.
    • Montalban G, Fraile-Bethencourt E, López-Perolio I, Pérez-Segura P, Infante M, Durán M, Alonso-Cerezo MC, López-Fernández A, Diez O, de la Hoya M, Velasco EA, Gutiérrez-Enríquez S.
    • Hum Mutat. 2018 Sep;39(9):1155-1160. doi: 10.1002/humu.23583. Epub 2018 Jul 13.
    • RNA analysis of cancer predisposing genes in formalin-fixed paraffin-embedded tissue determines aberrant splicing.
    • Jansen AM, van der Klift HM, Roos MA, van Eendenburg JD, Tops CM, Wijnen JT, Hes FJ, Morreau H, van Wezel T.
    • Eur J Hum Genet. 2018 Aug;26(8):1143-1150. doi: 10.1038/s41431-018-0153-z. Epub 2018 Apr 30.
    • Managing Variant Interpretation Discrepancies in Hereditary Cancer: Clinical Practice, Concerns, and Desired Resources.
    • Zirkelbach E, Hashmi S, Ramdaney A, Dunnington L, Ashfaq M, Nugent EK, Wilson K.
    • J Genet Couns. 2018 Aug;27(4):761-769. doi: 10.1007/s10897-017-0184-6. Epub 2017 Dec 20.
    • Quantitative Analysis of BRCA1 and BRCA2 Germline Splicing Variants Using a Novel RNA-Massively Parallel Sequencing Assay.
    • Farber-Katz S, Hsuan V, Wu S, Landrith T, Vuong H, Xu D, Li B, Hoo J, Lam S, Nashed S, Toppmeyer D, Gray P, Haynes G, Lu HM, Elliott A, Tippin Davis B, Karam R.
    • Front Oncol. 2018 Jul 27;8:286. doi: 10.3389/fonc.2018.00286. eCollection 2018.
    • A new bioinformatics tool to help assess the significance of BRCA1 variants.
    • Cusin I, Teixeira D, Zahn-Zabal M, Rech de Laval V, Gleizes A, Viassolo V, Chappuis PO, Hutter P, Bairoch A, Gaudet P.
    • Hum Genomics. 2018 Jul 11;12(1):36. doi: 10.1186/s40246-018-0168-0.
    • From the laboratory to the clinic: sharing BRCA VUS reclassification tools with practicing genetics professionals.
    • Augusto BM, Lake P, Scherr CL, Couch FJ, Lindor NM, Vadaparampil ST.
    • J Community Genet. 2018 Jul;9(3):209-215. doi: 10.1007/s12687-017-0343-3. Epub 2017 Nov 9.
    • Evaluation of some direct-to-consumer genetic testing reveals inaccuracies and misinterpretations.
    • [No author given]
    • FORCE. XRAYS. 2018 Jun 28.

    Related:

    False-positive results released by direct-to-consumer genetic tests highlight the importance of clinical confirmation testing for appropriate patient care.

    • Increased centrosome number in BRCA-related breast cancer specimens determined by immunofluorescence analysis.
    • Watanabe G, Chiba N, Nomizu T, Furuta A, Sato K, Miyashita M, Tada H, Suzuki A, Ohuchi N, Ishida T.
    • Cancer Sci. 2018 Jun;109(6):2027-2035. doi: 10.1111/cas.13595. Epub 2018 May 15.
    • Identification of Eight Spliceogenic Variants in BRCA2 Exon 16 by Minigene Assays.
    • Fraile-Bethencourt E, Valenzuela-Palomo A, Díez-Gómez B, Acedo A, Velasco EA.
    • Front Genet. 2018 May 24;9:188. doi: 10.3389/fgene.2018.00188. eCollection 2018.
    • Investigation of Experimental Factors That Underlie BRCA1/2 mRNA Isoform Expression Variation: Recommendations for Utilizing Targeted RNA Sequencing to Evaluate Potential Spliceogenic Variants.
    • Lattimore VL, Pearson JF, Currie MJ, Spurdle AB; kConFab Investigators, Robinson BA, Walker LC.
    • Front Oncol. 2018 May 3;8:140. doi: 10.3389/fonc.2018.00140. eCollection 2018.
    • BRCA1/2 germline missense mutations: a systematic review.
    • Corso G, Feroce I, Intra M, Toesca A, Magnoni F, Sargenti M, Naninato P, Caldarella P, Pagani G, Vento A, Veronesi P, Bonanni B, Galimberti V.
    • Eur J Cancer Prev. 2018 May;27(3):279-286. doi: 10.1097/CEJ.0000000000000337.
    • Review
    • The BRCA2 c.68-7T > A variant is not pathogenic: A model for clinical calibration of spliceogenicity.
    • Colombo M, Lòpez-Perolio I, Meeks HD, Caleca L, Parsons M, Li H, De Vecchi G, Tudini E, Foglia C, Mondini P, Manoukian S, Behar R, Garcia EBG, Meindl A, Montagna M, Niederacher D, Schmidt AY, Varesco L, Wappenschmidt B, Bolla MK, Dennis J, Michailidou K, Wang Q, Aittomäki K, Andrulis IL, Anton-Culver H, Arndt V, Beckmann MW, Beeghly-Fadel A, Benitez J, Boeckx B, Bogdanova NV, Bojesen SE, Bonanni B, Brauch H, Brenner H, Burwinkel B, Chang-Claude J, Conroy DM, Couch FJ, Cox A, Cross SS, Czene K, Devilee P, Dörk T, Eriksson M, Fasching PA, Figueroa J, Fletcher O, Flyger H, Gabrielson M, García-Closas M, Giles GG, González-Neira A, Guénel P, Haiman CA, Hall P, Hamann U, Hartman M, Hauke J, Hollestelle A, Hopper JL, Jakubowska A, Jung A, Kosma VM, Lambrechts D, Marchand LL, Lindblom A, Lubinski J, Mannermaa A, Margolin S, Miao H, Milne RL, Neuhausen SL, Nevanlinna H, Olson JE, Peterlongo P, Peto J, Pylkäs K, Sawyer EJ, Schmidt MK, Schmutzler RK, Schneeweiss A, Schoemaker MJ, See MH, Southey MC, Swerdlow A, Teo SH, Toland AE, Tomlinson I, Truong T, van Asperen CJ, van den Ouweland AMW, van der Kolk L, Winqvist R, Yannoukakos D, Zheng W; kConFab/AOCS Investigators, Dunning AM, Easton DF, Henderson A, Hogervorst F, Izatt L, Offitt K, Side LE, van Rensburg EJ, Embrace S, Hebon S, McGuffog L, Antoniou AC, Chenevix-Trench G, Spurdle AB, Goldgar DE, de la Hoya M, Radice P.
    • Hum Mutat. 2018 May;39(5):729-741. doi: 10.1002/humu.23411. Epub 2018 Apr 6.
    • Preliminary molecular evidence associating a novel BRCA1 synonymous variant with hereditary ovarian cancer syndrome.
    • Minucci A, Concolino P, De Bonis M, Costella A, Paris I, Scambia G, Capoluongo E.
    • Hum Genome Var. 2018 Apr 20;5:2. doi: 10.1038/s41439-018-0003-0. eCollection 2018.
    • Pathogenic Germline Variants in 10,389 Adult Cancers.
    • Huang KL, Mashl RJ, Wu Y, Ritter DI, Wang J, Oh C, Paczkowska M, Reynolds S, Wyczalkowski MA, Oak N, Scott AD, Krassowski M, Cherniack AD, Houlahan KE, Jayasinghe R, Wang LB, Zhou DC, Liu D, Cao S, Kim YW, Koire A, McMichael JF, Hucthagowder V, Kim TB, Hahn A, Wang C, McLellan MD, Al-Mulla F, Johnson KJ; Cancer Genome Atlas Research Network, Lichtarge O, Boutros PC, Raphael B, Lazar AJ, Zhang W, Wendl MC, Govindan R, Jain S, Wheeler D, Kulkarni S, Dipersio JF, Reimand J, Meric-Bernstam F, Chen K, Shmulevich I, Plon SE, Chen F, Ding L.
    • Cell. 2018 Apr 5;173(2):355-370.e14. doi: 10.1016/j.cell.2018.03.039.
    • Full in-frame exon 3 skipping of BRCA2 confers high risk of breast and/or ovarian cancer.
    • Caputo SM, Léone M, Damiola F, Ehlen A, Carreira A, Gaidrat P, Martins A, Brandão RD, Peixoto A, Vega A, Houdayer C, Delnatte C, Bronner M, Muller D, Castera L, Guillaud-Bataille M, Søkilde I, Uhrhammer N, Demontety S, Tubeuf H, Castelain G; French COVAR group collaborators, Jensen UB, Petitalot A, Krieger S, Lefol C, Moncoutier V, Boutry-Kryza N, Nielsen HR, Sinilnikova O, Stoppa-Lyonnet D, Spurdle AB, Teixeira MR, Coulet F, Thomassen M, Rouleau E.
    • Oncotarget. 2018 Apr 3;9(25):17334-17348. doi: 10.18632/oncotarget.24671. eCollection 2018 Apr 3.
    • Assessment of the functional impact of germline BRCA1/2 variants located in non-coding regions in families with breast and/or ovarian cancer predisposition.
    • Dos Santos ES, Caputo SM, Castera L, Gendrot M, Briaux A, Breault M, Krieger S, Rogan PK, Mucaki EJ, Burke LJ; ENIGMA consortium, Bièche I, Houdayer C, Vaur D, Stoppa-Lyonnet D, Brown MA, Lallemand F, Rouleau E.
    • Breast Cancer Res Treat. 2018 Apr;168(2):311-325. doi: 10.1007/s10549-017-4602-0. Epub 2017 Dec 13.
    • A comparison of cosegregation analysis methods for the clinical setting.
    • Rañola JMO, Liu Q, Rosenthal EA, Shirts BH.
    • Fam Cancer. 2018 Apr;17(2):295-302. doi: 10.1007/s10689-017-0017-7.
    • Thorough in silico and in vitro cDNA analysis of 21 putative BRCA1 and BRCA2 splice variants and a complex tandem duplication in BRCA2, allowing the identification of activated cryptic splice donor sites in BRCA2 exon 11.
    • Baert A, Machackova E, Coene I, Cremin C, Turner K, Portigal-Todd C, Asrat MJ, Nuk J, Mindlin A, Sean Y, MacMillan A, Van Maerken T, Trbusek M, McKinnon W, Wood ME, Foulkes WD, Santamariña M, de la Hoya M, Foretova L, Poppe B, Vral A, Rosseel T, De Leeneer K, Vega A, Claes KBM.
    • Hum Mutat. 2018 Apr;39(4):515-526. doi: 10.1002/humu.23390. Epub 2018 Jan 22.
    • Performance of in silico prediction tools for the classification of rare BRCA1/2 missense variants in clinical diagnostics.
    • Ernst C, Hahnen E, Engel C, Nothnagel M, Weber J, Schmutzler RK, Hauke J.
    • BMC Med Genomics. 2018 Mar 27;11(1):35. doi: 10.1186/s12920-018-0353-y.
    • False-positive results released by direct-to-consumer genetic tests highlight the importance of clinical confirmation testing for appropriate patient care.
    • Tandy-Connor S, Guiltinan J, Krempely K, LaDuca H, Reineke P, Gutierrez S, Gray P, Tippin Davis B.
    • Genet Med. 2018 Mar 22. doi: 10.1038/gim.2018.38. [Epub ahead of print]

    Related:

    Commentary:

    Attention: Direct-To-Consumer patrons: Proceed with caution.

    Research news: Evaluation of some direct-to-consumer genetic testing reveals inaccuracies and misinterpretations (FORCE. XRAYS.)

    Press: Wrangle Over DTC Results—Ambry Study Highlights 40% False Positives, 23andMe Defends Tests, and Experts Weigh In. (Clinical OMICs)

    Press: Ambry and My Gene Counsel Team Up on Tests to Confirm DTC Results, Counseling. (Clinical OMICs)

    • Data sharing as a national quality improvement program: reporting on BRCA1 and BRCA2 variant-interpretation comparisons through the Canadian Open Genetics Repository (COGR).
    • Lebo MS, Zakoor KR, Chun K, Speevak MD, Waye JS, McCready E, Parboosingh JS, Lamont RE, Feilotter H, Bosdet I, Tucker T, Young S, Karsan A, Charames GS, Agatep R, Spriggs EL, Chisholm C, Vasli N, Daoud H, Jarinova O, Tomaszewski R, Hume S, Taylor S, Akbari MR, Lerner-Ellis J; Canadian Open Genetics Repository Working Group.
    • Genet Med. 2018 Mar;20(3):294-302. doi: 10.1038/gim.2017.80. Epub 2017 Jul 20.
    • Clinical testing of BRCA1 and BRCA2: a worldwide snapshot of technological practices.
    • Toland AE, Forman A, Couch FJ, Culver JO, Eccles DM, Foulkes WD, Hogervorst FBL, Houdayer C, Levy-Lahad E, Monteiro AN, Neuhausen SL, Plon SE, Sharan SK, Spurdle AB, Szabo C, Brody LC; BIC Steering Committee.
    • NPJ Genom Med. 2018 Feb 15;3:7. doi: 10.1038/s41525-018-0046-7. eCollection 2018.
    • Assessment of the Clinical Relevance of BRCA2 Missense Variants by Functional and Computational Approaches.
    • Guidugli L, Shimelis H, Masica DL, Pankratz VS, Lipton GB, Singh N, Hu C, Monteiro ANA, Lindor NM, Goldgar DE, Karchin R, Iversen ES, Couch FJ.
    • Am J Hum Genet. 2018 Feb 1;102(2):233-248. doi: 10.1016/j.ajhg.2017.12.013. Epub 2018 Jan 25.
    • Combined annotation-dependent depletion score for BRCA1/2 variants in patients with breast and/or ovarian cancer.
    • Nakagomi H, Mochizuki H, Inoue M, Hirotsu Y, Amemiya K, Sakamoto I, Nakagomi S, Kubota T, Omata M.
    • Cancer Sci. 2018 Feb;109(2):453-461. doi: 10.1111/cas.13464. Epub 2018 Jan 17.
    • Genetic variants of prospectively demonstrated phenocopies in BRCA1/2 kindreds.
    • Dominguez-Valentin M, Evans DGR, Nakken S, Tubeuf H, Vodak D, Ekstrøm PO, Nissen AM, Morak M, Holinski-Feder E, Martins A, Møller P, Hovig E.
    • Hered Cancer Clin Pract. 2018 Jan 15;16:4. doi: 10.1186/s13053-018-0086-0. eCollection 2018.
    • ActiveDriverDB: human disease mutations and genome variation in post-translational modification sites of proteins.
    • Krassowski M, Paczkowska M, Cullion K, Huang T, Dzneladze I, Ouellette BFF, Yamada JT, Fradet-Turcotte A, Reimand J.
    • Nucleic Acids Res. 2018 Jan 4;46(D1):D901-D910. doi: 10.1093/nar/gkx973.
    • A Danish national effort of BRCA1/2 variant classification.
    • Pedersen IS, Schmidt AY, Bertelsen B, Ernst A, Andersen CLT, Kruse T, Rossing M, Thomassen M.
    • Acta Oncol. 2018 Jan;57(1):159-162. doi: 10.1080/0284186X.2017.1400693. Epub 2017 Nov 23.
    • Optimizing the identification of risk-relevant mutations by multigene panel testing in selected hereditary breast/ovarian cancer families.
    • Coppa A, Nicolussi A, D'Inzeo S, Capalbo C, Belardinilli F, Colicchia V, Petroni M, Zani M, Ferraro S, Rinaldi C, Buffone A, Bartolazzi A, Screpanti I, Ottini L, Giannini G.
    • Cancer Med. 2018 Jan;7(1):46-55. doi: 10.1002/cam4.1251. Epub 2017 Dec 22.
    • Mutation Screening of 10 Cancer Susceptibility Genes in Unselected Breast Cancer Patients.
    • Xie Y, Guoli L, Chen M, Guo X, Tang L, Luo X, Wang S, Yi W, Dai L, Wang J.
    • Clin Genet. 2018 Jan;93(1):41-51. doi: 10.1111/cge.13063. Epub 2017 Sep 25.
    • SABCS 2017 pathology: from bench to bedside.
    • Bago-Horvath Z.
    • Memo. 2018;11(3):217-219. doi: 10.1007/s12254-018-0427-8. Epub 2018 Aug 15.
    • Multiplex PCR and NGS-based identification of mRNA splicing variants: Analysis of BRCA1 splicing pattern as a model.
    • Hojny J, Zemankova P, Lhota F, Sevcik J, Stranecky V, Hartmannova H, Hodanova K, Mestak O, Pavlista D, Janatova M, Soukupova J, Vocka M, Kleibl Z, Kleiblova P.
    • Gene. 2017 Dec 30;637:41-49. doi: 10.1016/j.gene.2017.09.025. Epub 2017 Sep 14.
    • Nanopore sequencing of full-length BRCA1 mRNA transcripts reveals co-occurrence of known exon skipping events.
    • de Jong LC, Cree S, Lattimore V, Wiggins GAR, Spurdle AB; kConFab Investigators, Miller A, Kennedy MA, Walker LC.
    • Breast Cancer Res. 2017 Nov 28;19(1):127. doi: 10.1186/s13058-017-0919-1.
    • BRCA1/2 missense mutations and the value of in-silico analyses.
    • Sadowski CE, Kohlstedt D, Meisel C, Keller K, Becker K, Mackenroth L, Rump A, Schröck E, Wimberger P, Kast K.
    • Eur J Med Genet. 2017 Nov;60(11):572-577. doi: 10.1016/j.ejmg.2017.08.005. Epub 2017 Aug 12.
    • DNA repair-related functional assays for the classification of BRCA1 and BRCA2 variants: a critical review and needs assessment.
    • Toland AE, Andreassen PR.
    • J Med Genet. 2017 Nov;54(11):721-731. doi: 10.1136/jmedgenet-2017-104707. Epub 2017 Sep 2.
    • Functional analysis of BRCT missense mutations in BRCA1-mutated Chinese Han familial breast cancer.
    • Zhang H, Li L, Wang Y, Yin CC, Xie Y, Liu X, Ding H, Tian Z, Shen J, He L, Xia M, Ma X, Wu L.
    • Oncol Lett. 2017 Nov;14(5):5839-5844. doi: 10.3892/ol.2017.7003. Epub 2017 Sep 19.
    • Identification of a Novel BRCA1 Pathogenic Mutation in Korean Patients Following Reclassification of BRCA1 and BRCA2 Variants According to the ACMG Standards and Guidelines Using Relevant Ethnic Controls.
    • Park JS, Nam EJ, Park HS, Han JW, Lee JY, Kim J, Kim TI, Lee ST.
    • Cancer Res Treat. 2017 Oct;49(4):1012-1021. doi: 10.4143/crt.2016.433. Epub 2017 Jan 17.
    • Detecting splicing patterns in genes involved in hereditary breast and ovarian cancer.
    • Davy G, Rousselin A, Goardon N, Castéra L, Harter V, Legros A, Muller E, Fouillet R, Brault B, Smirnova AS, Lemoine F, de la Grange P, Guillaud-Bataille M, Caux-Moncoutier V, Houdayer C, Bonnet F, Blanc-Fournier C, Gaildrat P, Frebourg T, Martins A, Vaur D, Krieger S.
    • Eur J Hum Genet. 2017 Oct;25(10):1147-1154. doi: 10.1038/ejhg.2017.116. Epub 2017 Jul 26.
    • Identification and Characterization of a New BRCA2 Rearrangement in an Italian Family with Hereditary Breast and Ovarian Cancer Syndrome.
    • Concolino P, Rizza R, Hackmann K, Minucci A, Scaglione GL, De Bonis M, Costella A, Zuppi C, Schrock E, Capoluongo E.
    • Mol Diagn Ther. 2017 Oct;21(5):539-545. doi: 10.1007/s40291-017-0288-6.
    • Case report
    • Characterisation of the novel deleterious RAD51C p.Arg312Trp variant and prioritisation criteria for functional analysis of RAD51C missense changes.
    • Gayarre J, Martín-Gimeno P, Osorio A, Paumard B, Barroso A, Fernández V, de la Hoya M, Rojo A, Caldés T, Palacios J, Urioste M, Benítez J, García MJ.
    • Br J Cancer. 2017 Sep 26;117(7):1048-1062. doi: 10.1038/bjc.2017.286. Epub 2017 Aug 22.
    • Blind prediction of deleterious amino acid variations with SNPs&GO.
    • Capriotti E, Martelli PL, Fariselli P, Casadio R.
    • Hum Mutat. 2017 Sep;38(9):1064-1071. doi: 10.1002/humu.23179. Epub 2017 May 2.
    • A comparative study of germline BRCA1 and BRCA2 mutation screening methods in use in 20 European clinical diagnostic laboratories.
    • Ellison G, Wallace A, Kohlmann A, Patton S.
    • Br J Cancer. 2017 Aug 22;117(5):710-716. doi: 10.1038/bjc.2017.223. Epub 2017 Jul 27.
    • Next-Generation Sequencing in Order to Better Characterize a BRCA Variant of Uncertain Significance.
    • Sorscher S, Ramkissoon S.
    • Case Rep Oncol. 2017 Jul 11;10(2):634-637. doi: 10.1159/000478005. eCollection 2017 May-Aug.
    • Consistency of BRCA1 and BRCA2 Variant Classifications Among Clinical Diagnostic Laboratories.
    • Lincoln SE, Yang S, Cline MS, Kobayashi Y, Zhang C, Topper S, Haussler D, Paten B, Nussbaum RL.
    • JCO Precis Oncol. 2017 Jul;1. doi: 10.1200/PO.16.00020. Epub 2017 Apr 11.
    • Clinical Variant Classification: A Comparison of Public Databases and a Commercial Testing Laboratory.
    • Gradishar W, Johnson K, Brown K, Mundt E, Manley S.
    • Oncologist. 2017 Jul;22(7):797-803. doi: 10.1634/theoncologist.2016-0431. Epub 2017 Apr 13.

    Related:

    Letter, Comment:

    ClinVar Is a Critical Resource to Advance Variant Interpretation.

    Letter, Reply:

    In Reply.

    • BRCA2 Hypomorphic Missense Variants Confer Moderate Risks of Breast Cancer.
    • Shimelis H, Mesman RLS, Von Nicolai C, Ehlen A, Guidugli L, Martin C, Calléja FMGR, Meeks H, Hallberg E, Hinton J, Lilyquist J, Hu C, Aalfs CM, Aittomäki K, Andrulis I, Anton-Culver H, Arndt V, Beckmann MW, Benitez J, Bogdanova NV, Bojesen SE, Bolla MK, Borresen-Dale AL, Brauch H, Brennan P, Brenner H, Broeks A, Brouwers B, Brüning T, Burwinkel B, Chang-Claude J, Chenevix-Trench G, Cheng CY3, Choi JY, Collée JM, Cox A, Cross SS, Czene K, Darabi H, Dennis J, Dörk T, Dos-Santos-Silva I, Dunning AM, Fasching PA, Figueroa J, Flyger H, García-Closas M, Giles GG, Glendon G, Guénel P, Haiman CA, Hall P, Hamann U, Hartman M, Hogervorst FB, Hollestelle A, Hopper JL, Ito H, Jakubowska A, Kang D, Kosma VM, Kristensen V, Lai KN, Lambrechts D, Marchand LL, Li J, Lindblom A, Lophatananon A, Lubinski J, Machackova E, Mannermaa A, Margolin S, Marme F, Matsuo K, Miao H, Michailidou K, Milne RL, Muir K, Neuhausen SL, Nevanlinna H, Olson JE, Olswold C, Oosterwijk JJC, Osorio A, Peterlongo P, Peto J, Pharoah PDP, Pylkäs K, Radice P, Rashid MU, Rhenius V, Rudolph A, Sangrajrang S, Sawyer EJ, Schmidt MK, Schoemaker MJ, Seynaeve C, Shah M, Shen CY, Shrubsole M, Shu XO, Slager S, Southey MC, Stram DO, Swerdlow A, Teo SH, Tomlinson I, Torres D, Truong T, van Asperen CJ, van der Kolk LE, Wang Q, Winqvist R, Wu AH, Yu JC, Zheng W, Zheng Y, Leary J, Walker L, Foretova L, Fostira F, Claes KBM, Varesco L, Moghadasi S, Easton DF, Spurdle A, Devilee P, Vrieling H, Monteiro ANA, Goldgar DE, Carreira A, Vreeswijk MPG, Couch FJ; for kConFab/AOCS Investigators; for NBCS Collaborators.
    • Cancer Res. 2017 Jun 1;77(11):2789-2799. doi: 10.1158/0008-5472.CAN-16-2568. Epub 2017 Mar 10.
    • Validation and optimization of the Ion Torrent S5 XL sequencer and Oncomine workflow for BRCA1 and BRCA2 genetic testing.
    • Shin S, Kim Y, Oh SC, Yu N, Lee ST, Choi JR, Lee KA.
    • Oncotarget. 2017 May 23;8(21):34858-34866. doi: 10.18632/oncotarget.16799.
    • Power of pedigree likelihood analysis in extended pedigrees to classify rare variants of uncertain significance in cancer risk genes.
    • Rosenthal EA, Ranola JMO, Shirts BH.
    • Fam Cancer. 2017 May 22. doi: 10.1007/s10689-017-9989-6. [Epub ahead of print]
    • Variant effect prediction tools assessed using independent, functional assay-based datasets: implications for discovery and diagnostics.
    • Mahmood K, Jung CH, Philip G, Georgeson P, Chung J, Pope BJ, Park DJ.
    • Hum Genomics. 2017 May 16;11(1):10. doi: 10.1186/s40246-017-0104-8.
    • [China expert consensus on BRCA variant interpretation].
    • Panel members of China expert consensus on BRCA variant interpretation.
    • Zhonghua Bing Li Xue Za Zhi. 2017 May 8;46(5):293-297. doi: 10.3760/cma.j.issn.0529-5807.2017.05.002.
    • [Article in Chinese]
    • Assessment of in silico protein sequence analysis in the clinical classification of variants in cancer risk genes.
    • Kerr ID, Cox HC, Moyes K, Evans B, Burdett BC, van Kan A, McElroy H, Vail PJ, Brown KL, Sumampong DB, Monteferrante NJ, Hardman KL, Theisen A, Mundt E, Wenstrup RJ, Eggington JM.
    • J Community Genet. 2017 Apr;8(2):87-95. doi: 10.1007/s12687-016-0289-x. Epub 2017 Jan 3.
    • Functional classification of DNA variants by hybrid minigenes: Identification of 30 spliceogenic variants of BRCA2 exons 17 and 18.
    • Fraile-Bethencourt E, Díez-Gómez B, Velásquez-Zapata V, Acedo A, Sanz DJ, Velasco EA.
    • PLoS Genet. 2017 Mar 24;13(3):e1006691. doi: 10.1371/journal.pgen.1006691. eCollection 2017 Mar.
    • Characterization of BRCA1 and BRCA2 variants found in a Norwegian breast or ovarian cancer cohort.
    • Jarhelle E, Riise Stensland HM, Mæhle L, Van Ghelue M.
    • Fam Cancer. 2017 Jan;16(1):1-16. doi: 10.1007/s10689-016-9916-2.
    • A Lens for Evaluating Genetic Information Governance Models: Balancing Equity, Efficiency and Sustainability.
    • Skorve E, Vassilakopoulou P, Aanestad M, Grünfeld T.
    • Stud Health Technol Inform. 2017;235:298-302.
    • A Novel Pathogenic BRCA1 Splicing Variant Produces Partial Intron Retention in the Mature Messenger RNA.
    • Esposito MV, Nunziato M, Starnone F, Telese A, Calabrese A, D'Aiuto G, Pucci P, D'Aiuto M, Baralle F, D'Argenio V, Salvatore F.
    • Int J Mol Sci. 2016 Dec 21;17(12). pii: E2145. doi: 10.3390/ijms17122145.
    • Yeast cells reveal the misfolding and the cellular mislocalisation of the human BRCA1 protein.
    • Thouvenot P, Fourrière L, Dardillac E, Ben Yamin B, Lescure A, Lejour V, Heiligenstein X, Boulé JB, Romao M, Raposo-Benedetti G, Lopez BS, Nicolas A, Millot GA.
    • J Cell Sci. 2016 Dec 1;129(23):4366-4378. Epub 2016 Oct 17.

    Related:

    "In This Issue":

    Yeast cells detect human BRCA1 misfolding.

    • BRCA Share: A Collection of Clinical BRCA Gene Variants.
    • Beroud C, Letovsky SI, Braastad CD, Caputo SM, Beaudoux O, Bignon YJ, De Paillerets BB, Bronner M, Buell CM, Collod-Béroud G, Coulet F, Derive N, Divincenzo C, Elzinga CD, Garrec C, Houdayer C, Karbassi I, Lizard S, Love A, Muller D, Nagan N, Nery CR, Rai G, Revillion F, Salgado D, Sévenet N, Sinilnikova O, Sobol H, Stoppa-Lyonnet D, Toulas C, Trautman E, Vaur D, Vilquin P, Weymouth KS, Willis A; Laboratory Corporation of America Variant Classification Group; Quest Diagnostics Variant Classification Group; UNICANCER Genetic Group BRCA Laboratory Network, Eisenberg M, Strom CM.
    • Hum Mutat. 2016 Dec;37(12):1318-1328. doi: 10.1002/humu.23113. Epub 2016 Sep 28.
    • Conflicting Interpretation of Genetic Variants and Cancer Risk by Commercial Laboratories as Assessed by the Prospective Registry of Multiplex Testing.
    • Balmaña J, Digiovanni L, Gaddam P, Walsh MF, Joseph V, Stadler ZK, Nathanson KL, Garber JE, Couch FJ, Offit K, Robson ME, Domchek SM.
    • J Clin Oncol. 2016 Dec;34(34):4071-4078. Epub 2016 Sep 30.

    Related:

    Letter:

    Clinical Genetics Testing Laboratories Have a Remarkably Low Rate of Clinically Significant Discordance When Interpreting Variants in Hereditary Cancer Syndrome Genes.

    Letter:

    Reply to R. Nussbaum et al and J. Dolinsky et al.

    • As revenue falls, a pioneer of cancer gene testing slams rivals with overblown claims.
    • Sharon Begley
    • STAT. 2016 Nov 29.

    Related:

    Comments from NSGC Discussion Forum Cancer SIG

    Subject: Variant calling

    • Revisiting the morbid genome of Mendelian disorders.
    • Abouelhoda M, Faquih T, El-Kalioby M, Alkuraya FS.
    • Genome Biol. 2016 Nov 24;17(1):235.
    • In silico, in vitro and case-control analyses as an effective combination for analyzing BRCA1 and BRCA2 unclassified variants in a population-based sample.
    • Rodríguez-Balada M, Roig B, Martorell L, Melé M, Salvat M, Vilella E, Borràs J, Gumà J.
    • Cancer Genet. 2016 Nov;209(11):487-492. doi: 10.1016/j.cancergen.2016.09.003. Epub 2016 Sep 20.
    • Sensitivity of BRCA1/2 testing in high-risk breast/ovarian/male breast cancer families: little contribution of comprehensive RNA/NGS panel testing.
    • Byers H, Wallis Y, van Veen EM, Lalloo F, Reay K, Smith P, Wallace AJ, Bowers N, Newman WG, Evans DG.
    • Eur J Hum Genet. 2016 Nov;24(11):1591-1597. doi: 10.1038/ejhg.2016.57. Epub 2016 Jun 8.
    • HIPAA complaint alleges myriad genetics withheld variant data from patients: Allegation highlights the importance of data sharing, new HIPAA guidance.
    • [No authors listed]
    • Am J Med Genet A. 2016 Sep;170(9):2234-5. doi: 10.1002/ajmg.a.37886.
    • Molecular characterization, homology modeling and docking studies of the R2787H missense variation in BRCA2 gene: Association with breast cancer.
    • Riahi A, Messaoudi A, Mrad R, Fourati A, Chabouni-Bouhamed H, Kharrat M.
    • J Theor Biol. 2016 Aug 21;403:188-96. doi: 10.1016/j.jtbi.2016.05.013. Epub 2016 May 19.
    • Multi-gene Testing Increases Complexity of Counseling Women at Risk of Breast and Ovarian Cancer.
    • Hughes, D
    • Cancer Therapy Advisor. Breast Cancer Advisor. 2016 Jul 6.

    Related:

    Comments from NSGC Discussion Forum Cancer SIG

    Subject: VUS

    • Adding In Silico Assessment of Potential Splice Aberration to the Integrated Evaluation of BRCA Gene Unclassified Variants.
    • Vallée MP, Di Sera TL, Nix DA, Paquette AM, Parsons MT, Bell R, Hoffman A, Hogervorst FB, Goldgar DE, Spurdle AB, Tavtigian SV.
    • Hum Mutat. 2016 Jul;37(7):627-39. doi: 10.1002/humu.22973. Epub 2016 Apr 15.
    • Prioritizing Variants in Complete Hereditary Breast and Ovarian Cancer Genes in Patients Lacking Known BRCA Mutations.
    • Caminsky NG, Mucaki EJ, Perri AM, Lu R, Knoll JH, Rogan PK.
    • Hum Mutat. 2016 Jul;37(7):640-52. doi: 10.1002/humu.22972. Epub 2016 Mar 18.
    • Functional Assessment of Genetic Variants with Outcomes Adapted to Clinical Decision-Making.
    • Thouvenot P, Ben Yamin B, Fourrière L, Lescure A, Boudier T, Del Nery E, Chauchereau A, Goldgar DE, Houdayer C, Stoppa-Lyonnet D, Nicolas A, Millot GA.
    • PLoS Genet. 2016 Jun 6;12(6):e1006096. doi: 10.1371/journal.pgen.1006096. eCollection 2016.
    • Combined genetic and splicing analysis of BRCA1 c.[594-2A>C; 641A>G] highlights the relevance of naturally occurring in-frame transcripts for developing disease gene variant classification algorithms.
    • de la Hoya M, Soukarieh O, López-Perolio I, Vega A, Walker LC, van Ierland Y, Baralle D, Santamariña M, Lattimore V, Wijnen J, Whiley P, Blanco A, Raponi M, Hauke J, Wappenschmidt B, Becker A, Hansen TV, Behar R, Investigators K, Niederacher D, Arnold N, Dworniczak B, Steinemann D, Faust U, Rubinstein W, Hulick PJ, Houdayer C, Caputo SM, Castera L, Pesaran T, Chao E, Brewer C, Southey MC, van Asperen CJ, Singer CF, Sullivan J, Poplawski N, Mai P, Peto J, Johnson N, Burwinkel B, Surowy H, Bojesen SE, Flyger H, Lindblom A, Margolin S, Chang-Claude J, Rudolph A, Radice P, Galastri L, Olson JE, Hallberg E, Giles GG, Milne RL, Andrulis IL, Glendon G, Hall P, Czene K, Blows F, Shah M, Wang Q, Dennis J, Michailidou K, McGuffog L, Bolla MK, Antoniou AC, Easton DF, Couch FJ, Tavtigian S, Vreeswijk MP, Parsons M, Meeks HD, Martins A, Goldgar DE, Spurdle AB.
    • Hum Mol Genet. 2016 Jun 1;25(11):2256-2268. Epub 2016 Mar 23.
    • Exclusive: Breast cancer gene database gives clearer picture of risk.
    • Susan Miller.
    • USA Today. 2016 Jun 1.
    • Multigene testing of moderate-risk genes: be mindful of the missense.
    • Young EL, Feng BJ, Stark AW, Damiola F, Durand G, Forey N, Francy TC, Gammon A, Kohlmann WK, Kaphingst KA, McKay-Chopin S, Nguyen-Dumont T, Oliver J, Paquette AM, Pertesi M, Robinot N, Rosenthal JS, Vallee M, Voegele C, Hopper JL, Southey MC, Andrulis IL, John EM, Hashibe M, Gertz J; Breast Cancer Family Registry, Le Calvez-Kelm F, Lesueur F, Goldgar DE, Tavtigian SV.
    • J Med Genet. 2016 Jun;53(6):366-76. doi: 10.1136/jmedgenet-2015-103398. Epub 2016 Jan 19.
    • Variant classifications in BRCA1 and BRCA2: A systematic analysis of interlaboratory concordance.
    • Lincoln SE, Cline M, Yang S, Kobayashi Y, Zhang M, O'Leary E, Topper S, Paten B, Nussbaum R.
    • J Clin Oncol. 2016 May 20;34(15s):1592.
    • Conference abstract
    • Evaluation of ACMG-Guideline-Based Variant Classification of Cancer Susceptibility and Non-Cancer-Associated Genes in Families Affected by Breast Cancer.
    • Maxwell KN, Hart SN, Vijai J, Schrader KA, Slavin TP, Thomas T, Wubbenhorst B, Ravichandran V, Moore RM, Hu C, Guidugli L, Wenz B, Domchek SM, Robson ME, Szabo C, Neuhausen SL, Weitzel JN, Offit K, Couch FJ, Nathanson KL.
    • Am J Hum Genet. 2016 May 5;98(5):801-817. doi: 10.1016/j.ajhg.2016.02.024.
    • A unified analytic framework for prioritization of non-coding variants of uncertain significance in heritable breast and ovarian cancer.
    • Mucaki EJ, Caminsky NG, Perri AM, Lu R, Laederach A, Halvorsen M, Knoll JH, Rogan PK.
    • BMC Med Genomics. 2016 Apr 11;9(1):19. doi: 10.1186/s12920-016-0178-5.
    • Classification and Clinical Management of Variants of Uncertain Significance in High Penetrance Cancer Predisposition Genes.
    • Moghadasi S, Eccles DM, Devilee P, Vreeswijk MP, van Asperen CJ.
    • Hum Mutat. 2016 Apr;37(4):331-6. doi: 10.1002/humu.22956. Epub 2016 Feb 5.
    • Editorial / Commentary
    • Medical implications of technical accuracy in genome sequencing.
    • Goldfeder RL, Priest JR, Zook JM, Grove ME, Waggott D, Wheeler MT, Salit M, Ashley EA.
    • Genome Med. 2016 Mar 2;8(1):24. doi: 10.1186/s13073-016-0269-0.
    • Beyond DNA: An Integrated and Functional Approach for Classifying Germline Variants in Breast Cancer Genes.
    • Pesaran T, Karam R, Huether R, Li S, Farber-Katz S, Chamberlin A, Chong H, LaDuca H, Elliott A.
    • Int J Breast Cancer. 2016;2016:2469523. Epub 2016 Oct 16.
    • BRCA2 Polymorphic Stop Codon K3326X and the Risk of Breast, Prostate, and Ovarian Cancers.
    • Meeks HD, Song H, Michailidou K, Bolla MK, Dennis J, Wang Q, Barrowdale D, Frost D; EMBRACE, McGuffog L, Ellis S, Feng B, Buys SS, Hopper JL, Southey MC, Tesoriero A; kConFab Investigators, James PA, Bruinsma F, Campbell IG; Australia Ovarian Cancer Study Group, Broeks A, Schmidt MK, Hogervorst FB; HEBON, Beckman MW, Fasching PA, Fletcher O, Johnson N, Sawyer EJ, Riboli E, Banerjee S, Menon U, Tomlinson I, Burwinkel B, Hamann U, Marme F, Rudolph A, Janavicius R, Tihomirova L, Tung N, Garber J, Cramer D, Terry KL, Poole EM, Tworoger SS, Dorfling CM, van Rensburg EJ, Godwin AK, Guénel P, Truong T; GEMO Study Collaborators, Stoppa-Lyonnet D, Damiola F, Mazoyer S, Sinilnikova OM, Isaacs C, Maugard C, Bojesen SE, Flyger H, Gerdes AM, Hansen TV, Jensen A, Kjaer SK, Hogdall C, Hogdall E, Pedersen IS, Thomassen M, Benitez J, González-Neira A, Osorio A, Hoya Mde L, Segura PP, Diez O, Lazaro C, Brunet J, Anton-Culver H, Eunjung L, John EM, Neuhausen SL, Ding YC, Castillo D, Weitzel JN, Ganz PA, Nussbaum RL, Chan SB, Karlan BY, Lester J, Wu A, Gayther S, Ramus SJ, Sieh W, Whittermore AS, Monteiro AN, Phelan CM, Terry MB, Piedmonte M, Offit K, Robson M, Levine D, Moysich KB, Cannioto R, Olson SH, Daly MB, Nathanson KL, Domchek SM, Lu KH, Liang D, Hildebrant MA, Ness R, Modugno F, Pearce L, Goodman MT, Thompson PJ, Brenner H, Butterbach K, Meindl A, Hahnen E, Wappenschmidt B, Brauch H, Brüning T, Blomqvist C, Khan S, Nevanlinna H, Pelttari LM, Aittomäki K, Butzow R, Bogdanova NV, Dörk T, Lindblom A, Margolin S, Rantala J, Kosma VM, Mannermaa A, Lambrechts D, Neven P, Claes KB, Maerken TV, Chang-Claude J, Flesch-Janys D, Heitz F, Varon-Mateeva R, Peterlongo P, Radice P, Viel A, Barile M, Peissel B, Manoukian S, Montagna M, Oliani C, Peixoto A, Teixeira MR, Collavoli A, Hallberg E, Olson JE, Goode EL, Hart SN, Shimelis H, Cunningham JM, Giles GG, Milne RL, Healey S, Tucker K, Haiman CA, Henderson BE, Goldberg MS, Tischkowitz M, Simard J, Soucy P, Eccles DM, Le N, Borresen-Dale AL, Kristensen V, Salvesen HB, Bjorge L, Bandera EV, Risch H, Zheng W, Beeghly-Fadiel A, Cai H, Pylkäs K, Tollenaar RA, Ouweland AM, Andrulis IL, Knight JA; OCGN, Narod S, Devilee P, Winqvist R, Figueroa J, Greene MH, Mai PL, Loud JT, García-Closas M, Schoemaker MJ, Czene K, Darabi H, McNeish I, Siddiquil N, Glasspool R, Kwong A, Park SK, Teo SH, Yoon SY, Matsuo K, Hosono S, Woo YL, Gao YT, Foretova L, Singer CF, Rappaport-Feurhauser C, Friedman E, Laitman Y, Rennert G, Imyanitov EN, Hulick PJ, Olopade OI, Senter L, Olah E, Doherty JA, Schildkraut J, Koppert LB, Kiemeney LA, Massuger LF, Cook LS, Pejovic T, Li J, Borg A, Öfverholm A, Rossing MA, Wentzensen N, Henriksson K, Cox A, Cross SS, Pasini BJ, Shah M, Kabisch M, Torres D, Jakubowska A, Lubinski J, Gronwald J, Agnarsson BA, Kupryjanczyk J, Moes-Sosnowska J, Fostira F, Konstantopoulou I, Slager S, Jones M; PRostate cancer AssoCiation group To Investigate Cancer Associated aLterations in the genome, Antoniou AC, Berchuck A, Swerdlow A, Chenevix-Trench G, Dunning AM, Pharoah PD, Hall P, Easton DF, Couch FJ, Spurdle AB, Goldgar DE.
    • J Natl Cancer Inst. 2015 Nov 19;108(2). pii: djv315. doi: 10.1093/jnci/djv315. Print 2016 Feb.

    Related:

    Comments on NSGC Discussion Forum Cancer SIG

    Subject: BRCA2 c.9976A>T classification

    • A workflow for the detection and classification of variants in the BRCA1 and BRCA2 genes.
    • Nickerson SL, Lai SW, Tang R, Prosser DO, Love DR.
    • Pathology. 2016 Feb;48 Suppl 1:S96. doi: 10.1016/j.pathol.2015.12.272. Epub 2016 Feb 25.
    • Exonic Splicing Mutations Are More Prevalent than Currently Estimated and Can Be Predicted by Using In Silico Tools.
    • Soukarieh O, Gaildrat P, Hamieh M, Drouet A, Baert-Desurmont S, Frébourg T, Tosi M, Martins A.
    • PLoS Genet. 2016 Jan 13;12(1):e1005756. doi: 10.1371/journal.pgen.1005756. eCollection 2016.

    Related:

    Research Highlight

    RNA: Exonic splicing mutation prevalence.

    • Investigating the effect of 28 BRCA1 and BRCA2 mutations on their related transcribed mRNA.
    • Quiles F, Menéndez M, Tornero E, del Valle J, Teulé À, Palanca S, Izquierdo A, Gómez C, Campos O, Santamaria R, Brunet J, Capellá G, Feliubadaló L, Lázaro C.
    • Breast Cancer Res Treat. 2016 Jan;155(2):215-22. doi: 10.1007/s10549-015-3674-y. Epub 2016 Jan 6.
    • Functional assays provide a robust tool for the clinical annotation of genetic variants of uncertain significance.
    • Woods NT, Baskin R, Golubeva V, Jhuraney A, De-Gregoriis G, Vaclova T, Goldgar DE, Couch FJ, Carvalho MA, Iversen ES, Monteiro AN.
    • NPJ Genom Med. 2016;1. pii: 16001. doi: 10.1038/npjgenmed.2016.1. Epub 2016 Mar 2.
    • DATA SHARING AND REPRODUCIBLE CLINICAL GENETIC TESTING: SUCCESSES AND CHALLENGES.
    • Yang S, Cline M, Zhang C, Paten B, Lincoln SE.
    • Pac Symp Biocomput. 2016;22:166-176.
    • Patterns and functional implications of rare germline variants across 12 cancer types.
    • Lu C, Xie M, Wendl MC, Wang J, McLellan MD, Leiserson MD, Huang KL, Wyczalkowski MA, Jayasinghe R, Banerjee T, Ning J, Tripathi P, Zhang Q, Niu B, Ye K, Schmidt HK, Fulton RS, McMichael JF, Batra P, Kandoth C, Bharadwaj M, Koboldt DC, Miller CA, Kanchi KL, Eldred JM, Larson DE, Welch JS, You M, Ozenberger BA, Govindan R, Walter MJ, Ellis MJ, Mardis ER, Graubert TA, Dipersio JF, Ley TJ, Wilson RK, Goodfellow PJ, Raphael BJ, Chen F, Johnson KJ, Parvin JD, Ding L.
    • Nat Commun. 2015 Dec 22;6:10086. doi: 10.1038/ncomms10086.

    Related:

    Press: Study Uncovers Inherited Genetic Susceptibility Across 12 Cancer Types? (DoveMed)

    • DNA methylation profiling to assess pathogenicity of BRCA1 unclassified variants in breast cancer.
    • Flower KJ, Shenker NS, El-Bahrawy M, Goldgar DE, Parsons MT; KConFab Investigators; Affect study group, Spurdle AB, Morris JR, Brown R, Flanagan JM.
    • Epigenetics. 2015 Dec 2;10(12):1121-32. doi: 10.1080/15592294.2015.1111504.
    • Exceptions to the rule: Case studies in the prediction of pathogenicity for genetic variants in hereditary cancer genes.
    • Rosenthal ET, Bowles KR, Pruss D, van Kan A, Vail PJ, McElroy H, Wenstrup RJ.
    • Clin Genet. 2015 Dec;88(6):533-41. doi: 10.1111/cge.12560. Epub 2015 Feb 11.
    • Functional Analysis of BARD1 Missense Variants in Homology-Directed Repair of DNA Double Strand Breaks.
    • Lee C, Banerjee T, Gillespie J, Ceravolo A, Parvinsmith MR, Starita LM, Fields S, Toland AE, Parvin JD.
    • Hum Mutat. 2015 Dec;36(12):1205-14. doi: 10.1002/humu.22902. Epub 2015 Sep 22.
    • Comparison of locus-specific databases for BRCA1 and BRCA2 variants reveals disparity in variant classification within and among databases.
    • Vail PJ, Morris B, van Kan A, Burdett BC, Moyes K, Theisen A, Kerr ID, Wenstrup RJ, Eggington JM.
    • J Community Genet. 2015 Oct;6(4):351-9. doi: 10.1007/s12687-015-0220-x. Epub 2015 Mar 18.
    • ClinGen and Genetic Testing.
    • Karam R, Pesaran T, Chao E.
    • N Engl J Med. 2015 Oct;373(14):1376-7. doi: 10.1056/NEJMc1508700#SA1.

    Related:

    ClinGen--the Clinical Genome Resource.

    Gene-panel sequencing and the prediction of breast-cancer risk.

    Comment / Letter

    ClinGen and Genetic Testing.

    Comment / Letter

    ClinGen and Genetic Testing.

    • Functional isogenic modeling of BRCA1 alleles reveals distinct carrier phenotypes.
    • Cochran RL, Cidado J, Kim M, Zabransky DJ, Croessmann S, Chu D, Wong HY, Beaver JA, Cravero K, Erlanger B, Parsons H, Heaphy CM, Meeker AK, Lauring J, Park BH.
    • Oncotarget. 2015 Sep 22;6(28):25240-51. doi: 10.18632/oncotarget.4595.
    • Meeting the challenges of interpreting variants of unknown clinical significance in BRCA testing.
    • Lattimore V, Currie M, Lintott C, Sullivan J, Robinson BA, Walker LC.
    • N Z Med J. 2015 Aug 7;128(1419):56-61.
    • Curating the Way to Better Determinants of Genetic Risk.
    • Phimister EG.
    • N Engl J Med. 2015 Jun 4;372(23):2227-2228. Epub 2015 May 27.
    • Editorial / Commentary
    • Gene-Panel Sequencing and the Prediction of Breast-Cancer Risk.
    • Easton DF, Pharoah PD, Antoniou AC, Tischkowitz M, Tavtigian SV, Nathanson KL, Devilee P, Meindl A, Couch FJ, Southey M, Goldgar DE, Evans DG, Chenevix-Trench G, Rahman N, Robson M, Domchek SM, Foulkes WD.
    • N Engl J Med. 2015 Jun 4;372(23):2243-2257. Epub 2015 May 27.

    Related:

    Comments on NSGC Discussion Forum Cancer SIG

    Subject: Excellent review paper in NEJM

    Comment / Letter

    ClinGen and Genetic Testing.

    • Functional variant analyses (FVAs) predict pathogenicity in the BRCA1 DNA double-strand break repair pathway.
    • Loke J, Pearlman A, Upadhyay K, Tesfa L, Shao Y, Ostrer H.
    • Hum Mol Genet. 2015 Jun 1;24(11):3030-7. doi: 10.1093/hmg/ddv048. Epub 2015 Feb 4.
    • Massively Parallel Functional Analysis of BRCA1 RING Domain Variants.
    • Starita LM, Young DL, Islam M, Kitzman JO, Gullingsrud J, Hause RJ, Fowler DM, Parvin JD, Shendure J, Fields S.
    • Genetics. 2015 Jun;200(2):413-22. doi: 10.1534/genetics.115.175802. Epub 2015 Mar 30.

    Related:

    Press: Study demonstrates potential of new approach for sorting out BRCA1 gene variants. (News Medical)

    • Behind the Scenes of Breast Cancer, Researchers Collect Genetic Clues in BRCA Database.
    • [No author given]
    • GlobeNewswire. 2015 May 7.
    • Predicting the Pathogenic Potential of BRCA1 and BRCA2 Gene Variants Identified in Clinical Genetic Testing.
    • Brookes C, Lai S, Doherty E, Love DR.
    • Sultan Qaboos Univ Med J. 2015 May;15(2):e218-25. Epub 2015 May 28.
    • BRCA Share (formerly UMD-BRCA1 mutations database) Home.
    • [No author given]
    • BRCA Share™ (formerly UMD-BRCA1 mutations database). 2015 Apr 21.
    • Splicing analysis of 14 BRCA1 missense variants classifies nine variants as pathogenic.
    • Ahlborn LB, Dandanell M, Steffensen AY, Jønson L, Nielsen FC, Hansen TV.
    • Breast Cancer Res Treat. 2015 Apr;150(2):289-98. doi: 10.1007/s10549-015-3313-7. Epub 2015 Feb 28.
    • Characterization of three alternative transcripts of the BRCA1 gene in patients with breast cancer and a family history of breast and/or ovarian cancer who tested negative for pathogenic mutations.
    • Gambino G, Tancredi M, Falaschi E, Aretini P, Caligo MA.
    • Int J Mol Med. 2015 Apr;35(4):950-6. doi: 10.3892/ijmm.2015.2103. Epub 2015 Feb 16.
    • BRCA1 Circos: a visualisation resource for functional analysis of missense variants.
    • Jhuraney A, Velkova A, Johnson RC, Kessing B, Carvalho RS, Whiley P, Spurdle AB, Vreeswijk MP, Caputo SM, Millot GA, Vega A, Coquelle N, Galli A, Eccles D, Blok MJ, Pal T, van der Luijt RB, Santamariña Pena M, Neuhausen SL, Donenberg T, Machackova E, Thomas S, Vallée M, Couch FJ, Tavtigian SV, Glover JN, Carvalho MA, Brody LC, Sharan SK, Monteiro AN; Evidence-based Network for the Interpretation of Germline Mutant Alleles Consortium.
    • J Med Genet. 2015 Apr;52(4):224-30. doi: 10.1136/jmedgenet-2014-102766. Epub 2015 Feb 2.
    • Functional Classification of BRCA2 DNA Variants by Splicing Assays in a Large Minigene with 9 Exons.
    • Acedo A, Hernández-Moro C, Curiel-García Á, Díez-Gómez B, Velasco EA.
    • Hum Mutat. 2015 Feb;36(2):210-21. doi: 10.1002/humu.22725.
    • Genome Annotation by Shotgun Inactivation of a Native Gene in Hemizygous Cells: Application to BRCA2 with Implication of Hypomorphic Variants.
    • Ghosh S, Bhunia AK, Paun BC, Gilbert SF, Dhru U, Patel K, Kern SE.
    • Hum Mutat. 2015 Feb;36(2):260-9. doi: 10.1002/humu.22736.

    Related:

    In This Issue"

    Shotgun approach to functional annotation of genes.

    • Refined histopathological predictors of BRCA1 and BRCA2 mutation status: a large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia.
    • Spurdle AB, Couch FJ, Parsons MT, McGuffog L, Barrowdale D, Bolla MK, Wang Q, Healey S, Schmutzler R, Wappenschmidt B, Rhiem K, Hahnen E, Engel C, Meindl A, Ditsch N, Arnold N, Plendl H, Niederacher D, Sutter C, Wang-Gohrke S, Steinemann D, Preisler-Adams S, Kast K, Varon-Mateeva R, Ellis S, Frost D, Platte R, Perkins J, Evans D, Izatt L, Eeles R, Adlard J, Davidson R, Cole T, Scuvera G, Manoukian S, Bonanni B, Mariette F, Fortuzzi S, Viel A, Pasini B, Papi L, Varesco L, Balleine R, Nathanson KL, Domchek SM, Offitt K, Jakubowska A, Lindor N, Thomassen M, Jensen U, Rantala J, Borg Å, Andrulis IL, Miron A, Hansen T, Caldes T, Neuhausen SL, Toland AE, Nevanlinna H, Montagna M, Garber J, Godwin AK, Osorio A, Factor RE, Terry MB, Rebbeck TR, Karlan BY, Southey M, Rashid M, Tung N, Pharoah P, Blows FM, Dunning AM, Provenzano E, Hall P, Czene K, Schmidt MK, Broeks A, Cornelissen S, Verhoef S, Fasching PA, Beckmann MW, Ekici AB, Slamon DJ, Bojesen SE, Nordestgaard BG, Nielsen SF, Flyger H, Chang-Claude J, Flesch-Janys D, Rudolph A, Seibold P, Aittomäki K, Muranen TA, Heikkilä P, Blomqvist C, Figueroa J, Chanock SJ, Brinton L, Lissowska J, Olson JE, Pankratz VS, John EM, Whittemore AS, West DW, Hamann U, Torres D, Ulmer H, Rüdiger T, Devilee P, Tollenaar R, Seynaeve C, Van Asperen CJ, Eccles DM, Tapper WJ, Durcan L, Jones L, Peto J, Dos-Santos-Silva I, Fletcher O, Johnson N, Dwek M, Swann R, Bane AL, Glendon G, Mulligan AM, Giles GG, Milne RL, Baglietto L, McLean C, Carpenter J, Clarke C, Scott R, Brauch H, Brüning T, Ko YD, Cox A, Cross SS, Reed M, Lubinski J, Jaworska-Bieniek K, Durda K, Gronwald J, Dörk T, Bogdanova N, Park-Simon TW, Hillemanns P, Haiman CA, Henderson BE, Schumacher F, Le Marchand L, Burwinkel B, Marme F, Surovy H, Yang R, Anton-Culver H, Ziogas A, Hooning MJ, Collée J, Martens J, Tilanus-Linthorst M, Brenner H, Dieffenbach A, Arndt V, Stegmaier C, Winqvist R, Pylkäs K, Jukkola-Vuorinen A, Grip M, Lindblom A, Margolin S, Joseph V, Robson M, Rau-Murthy R, González-Neira A, Arias J, Zamora P, Benítez J, Mannermaa A, Kataja V, Kosma VM, Hartikainen JM, Peterlongo P, Zaffaroni D, Barile M, Capra F, Radice P, Teo SH, Easton DF, Antoniou AC, Chenevix-Trench G, Goldgar DE; ABCTB Investigators; EMBRACE Group; GENICA Network; HEBON Group; kConFab Investigators.
    • Breast Cancer Res. 2014 Dec 23;16(6):3419. doi: 10.1186/s13058-014-0474-y.
    • Functional characterization of BRCA1 gene variants by mini-gene splicing assay.
    • Steffensen AY, Dandanell M, Jønson L, Ejlertsen B, Gerdes AM, Nielsen FC, Hansen TV.
    • Eur J Hum Genet. 2014 Dec;22(12):1362-1368. doi: 10.1038/ejhg.2014.40. Epub 2014 Mar 26.
    • An integrated in silico approach to analyze the involvement of single amino acid polymorphisms in FANCD1/BRCA2-PALB2 and FANCD1/BRCA2-RAD51 complex.
    • Doss CG, Nagasundaram N.
    • Cell Biochem Biophys. 2014 Nov;70(2):939-56. doi: 10.1007/s12013-014-0002-9.
    • An Efficient Pipeline for the Generation and Functional Analysis of Human BRCA2 Variants of Uncertain Significance.
    • Hendriks G, Morolli B, Calléja FM, Plomp A, Mesman RL, Meijers M, Sharan SK, Vreeswijk MP, Vrieling H.
    • Hum Mutat. 2014 Nov;35(11):1382-91. doi: 10.1002/humu.22678. Epub 2014 Sep 11.
    • Saturation editing of genomic regions by multiplex homology-directed repair.
    • Findlay GM, Boyle EA, Hause RJ, Klein JC, Shendure J.
    • Nature. 2014 Sep 4;513(7516):120-3. doi: 10.1038/nature13695.

    Related:

    Comment:

    Biological techniques: Edit the genome to understand it.

    Comment:

    Deep mutational scans with targeted editing

    Comment:

    Technology: testing all possibilities.

    Press: Translating mutation to function: Genome editing may revolutionise how we interpret our genomes. (PHG Foundation)

    • A comprehensive laboratory-based program for classification of variants of uncertain significance in hereditary cancer genes.
    • Eggington JM, Bowles KR, Moyes K, Manley S, Esterling L, Sizemore S, Rosenthal E, Theisen A, Saam J, Arnell C, Pruss D, Bennett J, Burbidge LA, Roa B, Wenstrup RJ.
    • Clin Genet. 2014 Sep;86(3):229-37. doi: 10.1111/cge.12315. Epub 2013 Dec 20.

    Related:

    Comments on NSGC Discussion Forum Cancer SIG

    Subject: PALB2 VUS

    Subject: MyRisk - anyone else feeling jipped?

    • Development and validation of a new algorithm for the reclassification of genetic variants identified in the BRCA1 and BRCA2 genes.
    • Pruss D, Morris B, Hughes E, Eggington JM, Esterling L, Robinson BS, van Kan A, Fernandes PH, Roa BB, Gutin A, Wenstrup RJ, Bowles KR.
    • Breast Cancer Res Treat. 2014 Aug;147(1):119-32. doi: 10.1007/s10549-014-3065-9. Epub 2014 Aug 2.
    • BRCA1 Exon 11, a CERES (Composite Regulatory Element of Splicing) Element Involved in Splice Regulation.
    • Tammaro C, Raponi M, Wilson DI, Baralle D.
    • Int J Mol Sci. 2014 Jul 23;15(7):13045-59. doi: 10.3390/ijms150713045.
    • BRCA1 Haploinsufficiency Leads to Altered Expression of Genes Involved in Cellular Proliferation and Development.
    • Feilotter HE, Michel C, Uy P, Bathurst L, Davey S.
    • PLoS One. 2014 Jun 20;9(6):e100068. doi: 10.1371/journal.pone.0100068. eCollection 2014.
    • The Truth about Public Genetic Databases.
    • [No author given]
    • Yale Cancer Genetic Counseling, 2014 Jun 16.
    • Cancer-gene data sharing boosted.
    • Hayden EC.
    • Nature. 2014 Jun 10;510(7504):198. doi: 10.1038/510198a.
    • Pathogenicity Evaluation of BRCA1 and BRCA2 Unclassified Variants Identified in Portuguese Breast/Ovarian Cancer Families.
    • Santos C, Peixoto A, Rocha P, Pinto P, Bizarro S, Pinheiro M, Pinto C, Henrique R, Teixeira MR.
    • J Mol Diagn. 2014 May;16(3):324-34. doi: 10.1016/j.jmoldx.2014.01.005. Epub 2014 Mar 5.
    • Estimating risks for variants of unknown significance according to their predicted pathogenicity classes with application to BRCA1.
    • Dowty JG, Lee E, McKean-Cowdin R, Henderson BE, Bernstein L, Ursin G, Hopper JL.
    • Breast Cancer Res Treat. 2014 Feb;144(1):171-7. doi: 10.1007/s10549-014-2845-6. Epub 2014 Jan 31.
    • Comparison of mRNA splicing assay protocols across multiple laboratories: recommendations for best practice in standardized clinical testing.
    • Whiley PJ, de la Hoya M, Thomassen M, Becker A, Brandão R, Pedersen IS, Montagna M, Menéndez M, Quiles F, Gutiérrez-Enríquez S, De Leeneer K, Tenés A, Montalban G, Tserpelis D, Yoshimatsu T, Tirapo C, Raponi M, Caldes T, Blanco A, Santamariña M, Guidugli L, de Garibay GR, Wong M, Tancredi M, Fachal L, Ding YC, Kruse T, Lattimore V, Kwong A, Chan TL, Colombo M, De Vecchi G, Caligo M, Baralle D, Lázaro C, Couch F, Radice P, Southey MC, Neuhausen S, Houdayer C, Fackenthal J, Hansen TV, Vega A, Diez O, Blok R, Claes K, Wappenschmidt B, Walker L, Spurdle AB, Brown MA; ENIGMA consortium.
    • Clin Chem. 2014 Feb;60(2):341-52. doi: 10.1373/clinchem.2013.210658. Epub 2013 Nov 8.
    • Functional Assays for Analysis of Variants of Uncertain Significance in BRCA2.
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    • Review
    • Multifactorial Likelihood Assessment of BRCA1 and BRCA2 Missense Variants Confirms That BRCA1:c.122A>G(p.His41Arg) Is a Pathogenic Mutation.
    • Whiley PJ, Parsons MT, Leary J, Tucker K, Warwick L, Dopita B, Thorne H, Lakhani SR, Goldgar DE, Brown MA, Spurdle AB.
    • PLoS One. 2014 Jan 28;9(1):e86836. doi: 10.1371/journal.pone.0086836. eCollection 2014.
    • Capillary Electrophoresis Analysis of Conventional Splicing Assays: IARC Analytical and Clinical Classification of 31 BRCA2 Genetic Variants.
    • de Garibay GR, Acedo A, García-Casado Z, Gutiérrez-Enríquez S, Tosar A, Romero A, Garre P, Llort G, Thomassen M, Díez O, Pérez-Segura P, Díaz-Rubio E, Velasco EA, Caldés T, de la Hoya M.
    • Hum Mutat. 2014 Jan;35(1):53-7. doi: 10.1002/humu.22456. Epub 2013 Oct 28.
    • Supreme Court Ruling Broadens BRCA Testing Options.
    • Azvolinsky A.
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    • My Cancer Story, My Genes, My Information.
    • Joanna Rudnick.
    • Huffington Post. The Blog. 2013 Nov 19.
    • Functional Analysis of a Large set of BRCA2 exon 7 Variants Highlights the Predictive Value of Hexamer Scores in Detecting Alterations of Exonic Splicing Regulatory Elements
    • Di Giacomo D, Gaildrat P, Abuli A, Abdat J, Frébourg T, Tosi M, Martins A.
    • Hum Mutat. 2013 Nov;34(11):1547-1557. doi: 10.1002/humu.22428. Epub 2013 Sep 18.
    • A High-Throughput Functional Complementation Assay for Classification of BRCA1 Missense Variants.
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    • Cancer Discov. 2013 Oct;3(10):1142-55. doi: 10.1158/2159-8290.CD-13-0094. Epub 2013 Jul 18.
    • Evaluation of a 5-tier scheme proposed for classification of sequence variants using bioinformatic and splicing assay data: inter-reviewer variability and promotion of minimum reporting guidelines.
    • Walker LC, Whiley PJ, Houdayer C, Hansen TV, Vega A, Santamarina M, Blanco A, Fachal L, Southey MC, Lafferty A, Colombo M, De Vecchi G, Radice P, Spurdle AB; ENIGMA consortium.
    • Hum Mutat. 2013 Oct;34(10):1424-31. doi: 10.1002/humu.22388. Epub 2013 Aug 13.
    • Meta-Analysis

    Related:

    Introductory article:

    Classifying the Effects of BRCA1 and BRCA2 Variants on Splicing - A Systematic Study.

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    • To Improve Care for Your High Risk HBOC Patients, You Don’t Need the Supreme Court: It Is All in Your Hands — and In Your Files.
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