ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.5465A>G (p.Asn1822Ser)

dbSNP: rs587781580
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001284432 SCV001470228 uncertain significance not provided 2020-03-05 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001348712 SCV001543022 uncertain significance Hereditary breast ovarian cancer syndrome 2024-04-27 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 1822 of the BRCA2 protein (p.Asn1822Ser). 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: 188431). 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%. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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 RCV002345560 SCV002651167 uncertain significance Hereditary cancer-predisposing syndrome 2024-11-01 criteria provided, single submitter clinical testing The p.N1822S variant (also known as c.5465A>G), located in coding exon 10 of the BRCA2 gene, results from an A to G substitution at nucleotide position 5465. The asparagine at codon 1822 is replaced by serine, an amino acid with highly similar properties. 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. Based on the available evidence, the clinical significance of this variant remains unclear.
University of Washington Department of Laboratory Medicine, University of Washington RCV002345560 SCV003848832 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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