ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.8309C>G (p.Ala2770Gly)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002430365 SCV002679312 uncertain significance Hereditary cancer-predisposing syndrome 2022-01-14 criteria provided, single submitter clinical testing The p.A2770G variant (also known as c.8309C>G), located in coding exon 17 of the BRCA2 gene, results from a C to G substitution at nucleotide position 8309. The alanine at codon 2770 is replaced by glycine, an amino acid with similar properties. This alteration was identified in 1/527 index patients with either breast, ovarian, or pancreatic cancer (Loizidou MA et al. Clin Genet, 2017 Apr;91:611-615). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV005097215 SCV005836287 uncertain significance Hereditary breast ovarian cancer syndrome 2024-02-06 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 2770 of the BRCA2 protein (p.Ala2770Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast and/or ovarian cancer (PMID: 27882536). ClinVar contains an entry for this variant (Variation ID: 1762854). 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 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.

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