ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.1160T>C (p.Val387Ala)

dbSNP: rs373945846
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000530126 SCV000635143 uncertain significance Hereditary breast ovarian cancer syndrome 2024-09-29 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 387 of the BRCA2 protein (p.Val387Ala). This variant is present in population databases (rs373945846, gnomAD 0.01%). 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: 462224). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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.
Color Diagnostics, LLC DBA Color Health RCV000771483 SCV000903946 likely benign Hereditary cancer-predisposing syndrome 2016-11-03 criteria provided, single submitter clinical testing
Ambry Genetics RCV000771483 SCV002620790 uncertain significance Hereditary cancer-predisposing syndrome 2023-08-30 criteria provided, single submitter clinical testing The p.V387A variant (also known as c.1160T>C), located in coding exon 9 of the BRCA2 gene, results from a T to C substitution at nucleotide position 1160. The valine at codon 387 is replaced by alanine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. 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 RCV000771483 SCV003849883 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 RCV003441925 SCV004170030 uncertain significance not provided 2023-05-11 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; Observed in a patient with breast cancer (Duzkale et al., 2021); This variant is associated with the following publications: (PMID: 31911673, 27767231, 29884841, 32377563, Duzkale_2021)

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