ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.230C>T (p.Thr77Ile)

dbSNP: rs1003162870
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000586172 SCV000694601 uncertain significance not provided 2017-04-07 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.230C>T (p.Thr77Ile) variant involves the alteration of a conserved nucleotide and is predicted to be damaging by 5/5 in silico tools. The variant is located in mitotic polo-like kinase 1-binding motif (Plk1) and the motif is conserved among diverse species. Plk1 is a key regulator of mitosis from mitotic initiation to cytokinesis.Plk1 is also required for appropriate localization of substrates. Studies have also revealed that Plk1 binds to the N-terminal region of BRCA2 and phosphorylates Ser193, and that this phosphorylation is enhanced as mitosis progresses (reviewed in Takaoka_2014). This variant is absent in 121186 control chromosomes from ExAC. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories. Another variant at this residue T77A has been classified as VUS by multiple submitters in ClinVar. Taken together, due to lack of clinical and functional information, this variant is classified as variant of uncertain significance (VUS) until additional information becomes available.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000586172 SCV004219536 uncertain significance not provided 2023-08-24 criteria provided, single submitter clinical testing To the best of our knowledge, this variant has not been reported in the published literature. It also 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 conflicting predictions that this variant is benign or damaging. Based on the available information, we are unable to determine the clinical significance of this variant.

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