ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.1543A>G (p.Thr515Ala)

gnomAD frequency: 0.00001  dbSNP: rs749469486
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000166164 SCV000216938 uncertain significance Hereditary cancer-predisposing syndrome 2023-08-29 criteria provided, single submitter clinical testing The p.T515A variant (also known as c.1543A>G), located in coding exon 9 of the BRCA2 gene, results from an A to G substitution at nucleotide position 1543. The threonine at codon 515 is replaced by alanine, an amino acid with similar properties. This amino acid position is poorly 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.
Invitae RCV000548268 SCV000635166 uncertain significance Hereditary breast ovarian cancer syndrome 2022-09-17 criteria provided, single submitter clinical testing 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. ClinVar contains an entry for this variant (Variation ID: 186550). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. This variant is present in population databases (rs749469486, gnomAD 0.007%). This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 515 of the BRCA2 protein (p.Thr515Ala).
GeneDx RCV002254912 SCV002526257 uncertain significance not provided 2022-05-24 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 1771A>G
University of Washington Department of Laboratory Medicine, University of Washington RCV000166164 SCV003851466 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).
All of Us Research Program, National Institutes of Health RCV003995484 SCV004818691 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2023-03-28 criteria provided, single submitter clinical testing

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