ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.1142A>G (p.Asp381Gly)

gnomAD frequency: 0.00001  dbSNP: rs769297468
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000701259 SCV000830050 uncertain significance Hereditary breast ovarian cancer syndrome 2022-04-08 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: 578294). This variant is also known as 1370A>G. This missense change has been observed in individual(s) with breast cancer (PMID: 23469205). This variant is present in population databases (rs769297468, gnomAD 0.0009%). This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 381 of the BRCA2 protein (p.Asp381Gly).
Ambry Genetics RCV001017418 SCV001178497 uncertain significance Hereditary cancer-predisposing syndrome 2024-02-01 criteria provided, single submitter clinical testing The p.D381G variant (also known as c.1142A>G), located in coding exon 9 of the BRCA2 gene, results from an A to G substitution at nucleotide position 1142. The aspartic acid at codon 381 is replaced by glycine, an amino acid with similar properties. One study identified this alteration in 1/54 Brazilian patients with early-onset breast cancer (Carraro DM et al. PLoS ONE, 2013 Mar;8:e57581). 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 RCV001017418 SCV003849866 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).

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