ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.5002G>A (p.Ala1668Thr)

gnomAD frequency: 0.00003  dbSNP: rs587782182
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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 RCV000130804 SCV000185700 uncertain significance Hereditary cancer-predisposing syndrome 2022-11-24 criteria provided, single submitter clinical testing The p.A1668T variant (also known as c.5002G>A), located in coding exon 10 of the BRCA2 gene, results from a G to A substitution at nucleotide position 5002. The alanine at codon 1668 is replaced by threonine, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV000821456 SCV000962212 uncertain significance Hereditary breast ovarian cancer syndrome 2025-01-07 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1668 of the BRCA2 protein (p.Ala1668Thr). This variant is present in population databases (rs587782182, gnomAD 0.007%). 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: 142019). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV000130804 SCV003852271 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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