ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.4593A>C (p.Lys1531Asn)

dbSNP: rs386833397
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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 RCV000509691 SCV000607883 uncertain significance Hereditary cancer-predisposing syndrome 2020-10-25 criteria provided, single submitter clinical testing The p.K1531N variant (also known as c.4593A>C), located in coding exon 10 of the BRCA2 gene, results from an A to C substitution at nucleotide position 4593. The lysine at codon 1531 is replaced by asparagine, an amino acid with 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV000792316 SCV000931603 uncertain significance Hereditary breast ovarian cancer syndrome 2019-06-19 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with BRCA2-related disease. ClinVar contains an entry for this variant (Variation ID: 441326). This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with asparagine at codon 1531 of the BRCA2 protein (p.Lys1531Asn). The lysine residue is highly conserved and there is a moderate physicochemical difference between lysine and asparagine.
University of Washington Department of Laboratory Medicine, University of Washington RCV000509691 SCV003850639 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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