ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.3049A>C (p.Ile1017Leu)

dbSNP: rs2072470931
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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 RCV001340278 SCV001534079 uncertain significance Hereditary breast ovarian cancer syndrome 2020-04-05 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with BRCA2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with leucine at codon 1017 of the BRCA2 protein (p.Ile1017Leu). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and leucine.
University of Washington Department of Laboratory Medicine, University of Washington RCV003158768 SCV003850336 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).
Ambry Genetics RCV003158768 SCV005102213 uncertain significance Hereditary cancer-predisposing syndrome 2024-05-17 criteria provided, single submitter clinical testing The p.I1017L variant (also known as c.3049A>C), located in coding exon 10 of the BRCA2 gene, results from an A to C substitution at nucleotide position 3049. The isoleucine at codon 1017 is replaced by leucine, an amino acid with highly similar properties. This variant was reported amongst 1666 individuals undergoing genetic testing based on a personal and/or family history of breast and/or ovarian cancer (Chapman-Davis E et al. J Gen Intern Med, 2021 Jan;36:35-42). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.

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