ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.4184C>T (p.Ala1395Val)

dbSNP: rs1782230124
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002024933 SCV002308469 uncertain significance Hereditary breast ovarian cancer syndrome 2021-11-04 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1395 of the BRCA2 protein (p.Ala1395Val). 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. 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. This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. This variant is not present in population databases (gnomAD no frequency).
University of Washington Department of Laboratory Medicine, University of Washington RCV003157075 SCV003848749 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).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003323973 SCV004029296 uncertain significance not specified 2023-07-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV003157075 SCV005026894 uncertain significance Hereditary cancer-predisposing syndrome 2024-01-12 criteria provided, single submitter clinical testing The p.A1395V variant (also known as c.4184C>T), located in coding exon 10 of the BRCA2 gene, results from a C to T substitution at nucleotide position 4184. The alanine at codon 1395 is replaced by valine, an amino acid with 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.

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