ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.5135G>A (p.Gly1712Glu)

dbSNP: rs1453037467
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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 RCV000798735 SCV000938365 uncertain significance Hereditary breast ovarian cancer syndrome 2024-04-30 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 1712 of the BRCA2 protein (p.Gly1712Glu). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 644751). 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.
Ambry Genetics RCV002334506 SCV002644733 uncertain significance Hereditary cancer-predisposing syndrome 2020-03-06 criteria provided, single submitter clinical testing The p.G1712E variant (also known as c.5135G>A), located in coding exon 10 of the BRCA2 gene, results from a G to A substitution at nucleotide position 5135. The glycine at codon 1712 is replaced by glutamic acid, an amino acid with similar properties. 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 RCV002334506 SCV003847020 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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