ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.4483G>A (p.Val1495Ile)

gnomAD frequency: 0.00003  dbSNP: rs80358680
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131290 SCV000186261 likely benign Hereditary cancer-predisposing syndrome 2019-11-13 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.
GeneDx RCV000212236 SCV000210336 likely benign not provided 2019-10-04 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 31131967)
Color Diagnostics, LLC DBA Color Health RCV000131290 SCV000903294 likely benign Hereditary cancer-predisposing syndrome 2015-08-09 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001401014 SCV001602825 likely benign Hereditary breast ovarian cancer syndrome 2024-12-24 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000131290 SCV002533874 uncertain significance Hereditary cancer-predisposing syndrome 2021-09-13 criteria provided, single submitter curation
University of Washington Department of Laboratory Medicine, University of Washington RCV000131290 SCV003850545 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).
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000212236 SCV005624433 uncertain significance not provided 2024-11-14 criteria provided, single submitter clinical testing The BRCA2 c.4483G>A (p.Val1495Ile) variant has been described as being likely benign in a multifactorial likelihood study (PMID: 31131967 (2019)), and reported to be located in a region of the BRCA2 gene that is tolerant to missense sequence changes (PMID: 31911673 (2020)). To the best of our knowledge, this variant has not been reported in individuals with BRCA2-related conditions in the published literature. The frequency of this variant in the general population, 0.000008 (2/250362 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. 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.
Breast Cancer Information Core (BIC) (BRCA2) RCV000113309 SCV000146434 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2000-06-12 no assertion criteria provided clinical testing

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