ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.4079A>G (p.Asp1360Gly)

dbSNP: rs730881529
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000160073 SCV000210329 uncertain significance not provided 2013-10-24 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.4079A>G at the cDNA level, p.Asp1360Gly (D1360G) at the protein level, and results in the change of an Aspartic Acid to a Glycine (GAT>GGT). This variant has not, to our knowledge, been published in the literature. BRCA2 Asp1360Gly was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This variant is a non-conservative substitution of a negative polar amino acid for a neutral non-polar one, altering a position that is highly variable throughout evolution and is not located in a known functional domain. In silico analyses predict this variant to have a benign effect on protein structure and function. Based on the currently available information, we consider BRCA2 Asp1360Gly to be a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV002295284 SCV002594696 uncertain significance Hereditary breast ovarian cancer syndrome 2023-05-22 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: 182206). 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). This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 1360 of the BRCA2 protein (p.Asp1360Gly).
University of Washington Department of Laboratory Medicine, University of Washington RCV003157430 SCV003848660 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).
Ambry Genetics RCV003157430 SCV003886460 uncertain significance Hereditary cancer-predisposing syndrome 2022-11-19 criteria provided, single submitter clinical testing The p.D1360G variant (also known as c.4079A>G), located in coding exon 10 of the BRCA2 gene, results from an A to G substitution at nucleotide position 4079. The aspartic acid at codon 1360 is replaced by glycine, 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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