ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.4892A>T (p.Lys1631Ile)

dbSNP: rs587781573
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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 RCV000129607 SCV000184394 uncertain significance Hereditary cancer-predisposing syndrome 2020-11-25 criteria provided, single submitter clinical testing The p.K1631I variant (also known as c.4892A>T), located in coding exon 10 of the BRCA2 gene, results from an A to T substitution at nucleotide position 4892. The lysine at codon 1631 is replaced by isoleucine, an amino acid with dissimilar properties. This amino acid position is not conserved in available vertebrate species from marmoset down. 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV000129607 SCV003852179 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).
Labcorp Genetics (formerly Invitae), Labcorp RCV003529989 SCV004319164 uncertain significance Hereditary breast ovarian cancer syndrome 2023-08-16 criteria provided, single submitter clinical testing 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: 141204). 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. This sequence change replaces lysine, which is basic and polar, with isoleucine, which is neutral and non-polar, at codon 1631 of the BRCA2 protein (p.Lys1631Ile). This variant is not present in population databases (gnomAD no frequency).

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