ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.2749G>A (p.Val917Ile)

dbSNP: rs1555282822
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000508368 SCV000600521 uncertain significance not specified 2016-12-14 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000816970 SCV000957502 uncertain significance Hereditary breast ovarian cancer syndrome 2023-11-11 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 917 of the BRCA2 protein (p.Val917Ile). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 438960). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA2 protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000508368 SCV002572475 uncertain significance not specified 2022-08-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV002438230 SCV002749329 uncertain significance Hereditary cancer-predisposing syndrome 2022-05-01 criteria provided, single submitter clinical testing The p.V917I variant (also known as c.2749G>A), located in coding exon 10 of the BRCA2 gene, results from a G to A substitution at nucleotide position 2749. The valine at codon 917 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
University of Washington Department of Laboratory Medicine, University of Washington RCV002438230 SCV003850107 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).
GeneDx RCV004722846 SCV005334979 uncertain significance not provided 2023-05-23 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; Has not been previously published as pathogenic or benign to our knowledge; Also known as 2977G>A
All of Us Research Program, National Institutes of Health RCV004802107 SCV005424344 uncertain significance BRCA2-related cancer predisposition 2024-03-05 criteria provided, single submitter clinical testing

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