ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.5264A>G (p.Glu1755Gly)

dbSNP: rs2137515724
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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 RCV001370851 SCV001567394 uncertain significance Hereditary breast ovarian cancer syndrome 2024-04-22 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 1755 of the BRCA2 protein (p.Glu1755Gly). 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: 1061297). 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 RCV002341801 SCV002643369 uncertain significance Hereditary cancer-predisposing syndrome 2022-06-20 criteria provided, single submitter clinical testing The p.E1755G variant (also known as c.5264A>G), located in coding exon 10 of the BRCA2 gene, results from an A to G substitution at nucleotide position 5264. The glutamic acid at codon 1755 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV002341801 SCV003847125 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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