ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.6950A>G (p.Asp2317Gly)

dbSNP: rs1555285332
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000562911 SCV000668544 uncertain significance Hereditary cancer-predisposing syndrome 2016-03-17 criteria provided, single submitter clinical testing The p.D2317G variant (also known as c.6950A>G), located in coding exon 12 of the BRCA2 gene, results from an A to G substitution at nucleotide position 6950. The aspartic acid at codon 2317 is replaced by glycine, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6495 samples (12990 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.0004% (greater than 225000 alleles tested) in our clinical cohort. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
KCCC/NGS Laboratory, Kuwait Cancer Control Center RCV003234783 SCV003932751 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2023-06-06 criteria provided, single submitter clinical testing BRCA2 c.6950A>G (p.Asp2317Gly) results in an amino acid change in position 2314. This variant has no entry in the population frequency database (gnomAD). ClinVar has a single entry for this variant and is described as of uncertain significance. As far as we know, this variant has not been published in individuals with cancer. In silico models are all in agreement this variant is deleterious. For these reasons, this mutation is considered as variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV003530076 SCV004263053 uncertain significance Hereditary breast ovarian cancer syndrome 2024-01-01 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 2317 of the BRCA2 protein (p.Asp2317Gly). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 482972). 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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