ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.784G>C (p.Ala262Pro)

gnomAD frequency: 0.00002  dbSNP: rs397507393
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000776409 SCV000911890 uncertain significance Hereditary cancer-predisposing syndrome 2019-01-05 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001302734 SCV001491954 uncertain significance Hereditary breast ovarian cancer syndrome 2024-03-12 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 262 of the BRCA2 protein (p.Ala262Pro). This variant is present in population databases (no rsID available, gnomAD 0.03%). 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: 630560). 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.
Sema4, Sema4 RCV000776409 SCV002531889 uncertain significance Hereditary cancer-predisposing syndrome 2021-10-28 criteria provided, single submitter curation
Ambry Genetics RCV000776409 SCV005097530 benign Hereditary cancer-predisposing syndrome 2024-06-04 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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