ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.3479G>A (p.Arg1160Lys)

gnomAD frequency: 0.00002  dbSNP: rs183920365
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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Vantari Genetics RCV000210809 SCV000267015 uncertain significance Hereditary cancer-predisposing syndrome 2016-01-21 criteria provided, single submitter clinical testing
Ambry Genetics RCV000210809 SCV000275029 likely benign Hereditary cancer-predisposing syndrome 2019-03-19 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: 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.
Invitae RCV000459507 SCV000549632 likely benign Hereditary breast ovarian cancer syndrome 2024-01-18 criteria provided, single submitter clinical testing
GeneDx RCV000521196 SCV000616971 uncertain significance not provided 2023-06-27 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Also known as 3707G>A; Observed in individuals with a personal and/or family history of breast cancer (Lara et al., 2012; Urbina-Jara et al., 2019); This variant is associated with the following publications: (PMID: 27656653, 31911673, 29884841, 32377563, 31658756, 33281875, 23096355, 30630528)
Counsyl RCV000082913 SCV000785773 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2017-11-27 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000210809 SCV000903832 likely benign Hereditary cancer-predisposing syndrome 2017-03-07 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000780007 SCV000916998 uncertain significance not specified 2022-10-13 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.3479G>A (p.Arg1160Lys) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 3.6e-05 in 250882 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.3479G>A has been reported in the literature in an individual affected with breast cancer, without strong evidence for causality (example, Poulet_2016). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Eight 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 (VUS, n=6; likely benign, n=2). Based on the evidence outlined above, the variant was classified as uncertain significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000521196 SCV001133755 uncertain significance not provided 2023-02-01 criteria provided, single submitter clinical testing The frequency of this variant in the general population, 0.00028 (10/35430 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. To the best of our knowledge, the variant has not been reported in individuals with a BRCA2 related disorder in the published literature. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.
Sema4, Sema4 RCV000210809 SCV002533800 uncertain significance Hereditary cancer-predisposing syndrome 2021-10-11 criteria provided, single submitter curation
University of Washington Department of Laboratory Medicine, University of Washington RCV000210809 SCV003846634 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) RCV000082913 SCV000114987 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2011-11-15 no assertion criteria provided clinical testing

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