ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.4769A>G (p.Lys1590Arg)

dbSNP: rs2072512459
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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 RCV001223675 SCV001395833 uncertain significance Hereditary breast ovarian cancer syndrome 2023-06-13 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 1590 of the BRCA2 protein (p.Lys1590Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer (PMID: 29020660). ClinVar contains an entry for this variant (Variation ID: 951700). 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 RCV002339592 SCV002634700 uncertain significance Hereditary cancer-predisposing syndrome 2022-03-29 criteria provided, single submitter clinical testing The p.K1590R variant (also known as c.4769A>G), located in coding exon 10 of the BRCA2 gene, results from an A to G substitution at nucleotide position 4769. The lysine at codon 1590 is replaced by arginine, an amino acid with highly similar properties. This alteration was identified in an individual diagnosed with breast and/or ovarian cancer (Santonocito C et al. Breast, 2017 Dec;36:74-78). 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV002339592 SCV003852083 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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