ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.4504C>G (p.Gln1502Glu)

dbSNP: rs1060502425
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000458369 SCV000549604 uncertain significance Hereditary breast ovarian cancer syndrome 2024-02-13 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 1502 of the BRCA2 protein (p.Gln1502Glu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast and/or colon cancer (PMID: 30093976). ClinVar contains an entry for this variant (Variation ID: 409486). 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000985527 SCV001133799 uncertain significance not provided 2019-04-21 criteria provided, single submitter clinical testing
Ambry Genetics RCV002339165 SCV002637606 uncertain significance Hereditary cancer-predisposing syndrome 2020-03-11 criteria provided, single submitter clinical testing The p.Q1502E variant (also known as c.4504C>G), located in coding exon 10 of the BRCA2 gene, results from a C to G substitution at nucleotide position 4504. The glutamine at codon 1502 is replaced by glutamic acid, an amino acid with highly similar properties. This alteration has been reported in a patient with breast cancer at age 41 and colon cancer at age 53 with a family history of colon and oral cancer (Chan GHJ et al. Oncotarget, 2018 Jul;9:30649-30660). 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 RCV002339165 SCV003850563 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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