ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.6257T>C (p.Ile2086Thr)

dbSNP: rs587783042
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000704093 SCV000833027 uncertain significance Hereditary breast ovarian cancer syndrome 2018-05-29 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: "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: 156489). This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with threonine at codon 2086 of the BRCA2 protein (p.Ile2086Thr). The isoleucine residue is weakly conserved and there is a moderate physicochemical difference between isoleucine and threonine.
University of Washington Department of Laboratory Medicine, University of Washington RCV003157413 SCV003852361 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 RCV003157413 SCV004005529 uncertain significance Hereditary cancer-predisposing syndrome 2023-06-05 criteria provided, single submitter clinical testing The p.I2086T variant (also known as c.6257T>C), located in coding exon 10 of the BRCA2 gene, results from a T to C substitution at nucleotide position 6257. The isoleucine at codon 2086 is replaced by threonine, 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV004998291 SCV005624490 uncertain significance not provided 2024-05-03 criteria provided, single submitter clinical testing The BRCA2 c.6257T>C (p.Ile2086Thr) variant has been reported in the published literature to be located in a region of the BRCA2 gene that is tolerant to missense sequence changes (PMID: 31911673 (2020)). To the best of our knowledge, this variant has not been reported in individuals with BRCA2-related disorders. This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.
Pathway Genomics RCV000144582 SCV000189899 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2014-07-24 no assertion criteria provided clinical testing

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