ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.6506C>T (p.Thr2169Ile)

dbSNP: rs1555284726
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000570270 SCV000668551 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-09 criteria provided, single submitter clinical testing The p.T2169I variant (also known as c.6506C>T), located in coding exon 10 of the BRCA2 gene, results from a C to T substitution at nucleotide position 6506. The threonine at codon 2169 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health RCV000570270 SCV000688983 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-05 criteria provided, single submitter clinical testing This missense variant replaces threonine with isoleucine at codon 2169 of the BRCA2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with BRCA2-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV000807789 SCV000947863 uncertain significance Hereditary breast ovarian cancer syndrome 2019-11-16 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: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 482975). This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with isoleucine at codon 2169 of the BRCA2 protein (p.Thr2169Ile). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and isoleucine.
University of Washington Department of Laboratory Medicine, University of Washington RCV000570270 SCV003852591 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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