ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.856T>C (p.Ser286Pro)

gnomAD frequency: 0.00001  dbSNP: rs80359111
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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001083702 SCV000073572 likely benign Hereditary breast ovarian cancer syndrome 2025-01-21 criteria provided, single submitter clinical testing
GeneDx RCV000589428 SCV000210550 likely benign not provided 2021-02-03 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 27225819, 24323938, 28263838, 25348012, 27062684, 24817641, 29061375, 26689913, 21671020, 23328489, 31131967)
Ambry Genetics RCV000163478 SCV000214033 likely benign Hereditary cancer-predisposing syndrome 2019-04-17 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Counsyl RCV000077446 SCV000488225 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2016-01-27 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000045559 SCV000602869 likely benign not specified 2017-02-27 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000163478 SCV000683984 likely benign Hereditary cancer-predisposing syndrome 2015-02-19 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000045559 SCV000695164 likely benign not specified 2024-11-11 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.856T>C (p.Ser286Pro) 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 variant allele was found at a frequency of 2.1e-05 in 240246 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.856T>C has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer (example: Balia 2011, Azzollini 2016, Solmaz_2020, Dorling_2021, Patruno_2021). These reports do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. Co-occurrences with pathogenic variants have been reported (BRCA1 c.5266dupC, p.Gln1756ProfsX74; BIC database) and have been observed internally (BRCA1 c.1044T>A, p.Cys348X), providing supporting evidence for a benign role. Several publications reported experimental evidence evaluating an impact on protein function (Balia 2011, Guidugli 2013, Spugnesi 2013). These results showed no damaging effect for this variant. The following publications have been ascertained in the context of this evaluation (PMID: 27062684, 21671020, 29061375, 33471991, 24323938, 26689913, 34572941, 31954625, 23328489, 28263838). ClinVar contains an entry for this variant (Variation ID: 52622). Based on the evidence outlined above, the variant was classified as likely benign.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000589428 SCV001470253 likely benign not provided 2023-05-15 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000163478 SCV002531959 likely benign Hereditary cancer-predisposing syndrome 2021-02-22 criteria provided, single submitter curation
University of Washington Department of Laboratory Medicine, University of Washington RCV000163478 SCV003848088 likely benign Hereditary cancer-predisposing syndrome 2023-03-23 criteria provided, single submitter curation Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
Sharing Clinical Reports Project (SCRP) RCV000077446 SCV000109244 likely benign Breast-ovarian cancer, familial, susceptibility to, 2 2013-03-04 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077446 SCV000145780 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2002-06-20 no assertion criteria provided clinical testing
BRCAlab, Lund University RCV000077446 SCV004244081 likely benign Breast-ovarian cancer, familial, susceptibility to, 2 2020-03-02 no assertion criteria provided clinical testing

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