ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.5737T>C (p.Cys1913Arg)

gnomAD frequency: 0.00002  dbSNP: rs80358799
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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000044738 SCV000072751 likely benign Hereditary breast ovarian cancer syndrome 2024-01-24 criteria provided, single submitter clinical testing
GeneDx RCV000586429 SCV000108628 likely benign not provided 2021-03-25 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 16683254, 26689913)
Ambry Genetics RCV000132499 SCV000187593 likely benign Hereditary cancer-predisposing syndrome 2018-04-30 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 RCV000031573 SCV000489248 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2016-09-09 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000212244 SCV000694896 likely benign not specified 2020-10-05 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.5737T>C (p.Cys1913Arg) 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 1.6e-05 in 250954 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.5737T>C has been reported in the literature in individuals affected with Breast cancer (example, Moghadasi_2013, Lu_2015). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. At-least one co-occurrence with another pathogenic variant has been reported in the BIC database (BRCA1 c.213-12A>G), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments (benign/likely benign, n=4). Based on the evidence outlined above, to reflect the emerging consensus in the clinical community, the variant was classified as likely benign.
Color Diagnostics, LLC DBA Color Health RCV000132499 SCV000903292 benign Hereditary cancer-predisposing syndrome 2017-03-08 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000586429 SCV001469439 uncertain significance not provided 2020-01-24 criteria provided, single submitter clinical testing
Genetics and Molecular Pathology, SA Pathology RCV002272032 SCV002556364 uncertain significance Familial cancer of breast 2022-06-07 criteria provided, single submitter clinical testing
University of Washington Department of Laboratory Medicine, University of Washington RCV000132499 SCV003849063 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) RCV000031573 SCV000054179 benign Breast-ovarian cancer, familial, susceptibility to, 2 2012-05-01 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031573 SCV000146683 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2000-08-16 no assertion criteria provided clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000586429 SCV000778690 uncertain significance not provided 2017-02-06 no assertion criteria provided clinical testing

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