ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.6745G>A (p.Ala2249Thr)

dbSNP: rs587781435
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129329 SCV000184092 uncertain significance Hereditary cancer-predisposing syndrome 2019-01-09 criteria provided, single submitter clinical testing The p.A2249T variant (also known as c.6745G>A) is located in coding exon 10 of the BRCA2 gene. This alteration results from a G to A substitution at nucleotide position 6745. The alanine at codon 2249 is replaced by threonine, an amino acid with similar properties. Based on protein sequence alignment, 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000637376 SCV000758832 uncertain significance Hereditary breast ovarian cancer syndrome 2025-02-01 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 2249 of the BRCA2 protein (p.Ala2249Thr). 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: 141013). 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.
Color Diagnostics, LLC DBA Color Health RCV000129329 SCV000906611 uncertain significance Hereditary cancer-predisposing syndrome 2019-05-31 criteria provided, single submitter clinical testing
University of Washington Department of Laboratory Medicine, University of Washington RCV000129329 SCV003847419 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).
All of Us Research Program, National Institutes of Health RCV003997494 SCV004844309 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2023-10-30 criteria provided, single submitter clinical testing

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