ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.1567C>A (p.His523Asn)

dbSNP: rs2072416501
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002028579 SCV002283744 uncertain significance Hereditary breast ovarian cancer syndrome 2021-06-05 criteria provided, single submitter clinical testing This sequence change replaces histidine with asparagine at codon 523 of the BRCA2 protein (p.His523Asn). The histidine residue is weakly conserved and there is a small physicochemical difference between histidine and asparagine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA2-related conditions. 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. 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.
Ambry Genetics RCV002398074 SCV002707235 likely benign Hereditary cancer-predisposing syndrome 2021-12-11 criteria provided, single submitter clinical testing This alteration is classified as likely 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV002398074 SCV003851490 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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