ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.943T>A (p.Cys315Ser) (rs79483201)

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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130455 SCV000185320 benign Hereditary cancer-predisposing syndrome 2015-05-08 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000112866 SCV000145791 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000769684 SCV000901097 likely benign Breast and/or ovarian cancer 2016-05-18 criteria provided, single submitter clinical testing
Color RCV000130455 SCV000684062 likely benign Hereditary cancer-predisposing syndrome 2015-06-01 criteria provided, single submitter clinical testing
Counsyl RCV000112866 SCV000220522 likely benign Breast-ovarian cancer, familial 2 2014-07-17 criteria provided, single submitter literature only
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000160200 SCV000591720 likely benign not specified 2016-08-10 criteria provided, single submitter clinical testing
GeneDx RCV000160200 SCV000210551 benign not specified 2016-06-21 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Illumina Clinical Services Laboratory,Illumina RCV000402194 SCV000383620 likely benign Fanconi anemia 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000045821 SCV000383621 likely benign Hereditary breast and ovarian cancer syndrome 2016-06-14 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000160200 SCV000916903 likely benign not specified 2018-06-05 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.943T>A (p.Cys315Ser) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 7 fold of the estimated maximal expected allele frequency for a pathogenic variant in BRCA2 causing Hereditary Breast and Ovarian Cancer phenotype (0.00075), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. c.943T>A has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer, but it was also present in several healthy controls at the same time (e.g. Ahmad 2012, Haiman 2013, Suter 2004). Moreover, recent case-control studies performed on South-East Asian cohorts indicated that the variant of interest was found with similar frequencies in breast cancer patients and healthy controls (Lai 2017, Yoon 2016). Co-occurrences with other pathogenic variants have also been reported (e.g. BRCA1 c.3810C>A, p.Cys1270X; in UMD), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Seven clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. These laboratories classified the variant as benign (3x) or likely benign (4x). Based on the evidence outlined above, the variant was classified as likely benign.
Invitae RCV000045821 SCV000073834 benign Hereditary breast and ovarian cancer syndrome 2018-01-12 criteria provided, single submitter clinical testing
Michigan Medical Genetics Laboratories,University of Michigan RCV000112866 SCV000267741 likely benign Breast-ovarian cancer, familial 2 2016-04-21 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000758976 SCV000887964 likely benign not provided 2017-12-20 criteria provided, single submitter clinical testing

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