ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.230C>T (p.Thr77Ile) (rs1003162870)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America 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.

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