ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.3671G>A (p.Gly1224Asp)

dbSNP: rs587782670
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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 RCV001231228 SCV001403741 uncertain significance Hereditary breast ovarian cancer syndrome 2024-04-29 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 1224 of the BRCA2 protein (p.Gly1224Asp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of BRCA2-related conditions (PMID: 34196900). ClinVar contains an entry for this variant (Variation ID: 958119). 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 RCV001800972 SCV002047059 uncertain significance not provided 2021-05-08 criteria provided, single submitter clinical testing
University of Washington Department of Laboratory Medicine, University of Washington RCV003158577 SCV003846782 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).
Ambry Genetics RCV003158577 SCV004849357 uncertain significance Hereditary cancer-predisposing syndrome 2019-09-06 criteria provided, single submitter clinical testing The c.3671G>A (p.G1224D) alteration is located in exon 11 (coding exon 10) of the BRCA2 gene. This alteration results from a G to A substitution at nucleotide position 3671, causing the glycine (G) at amino acid position 1224 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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