ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.943-2_1076+1del

dbSNP: rs2104242036
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001356810 SCV001552075 pathogenic Carcinoma of colon no assertion criteria provided clinical testing The c.943-?_1076+?del variant results in a deletion of exon 6 and is predicted to cause a frameshift, leading to a premature stop codon downstream (p.Gly315IlefsX29), although the precise breakpoints of this deletion were not determined, nor were the effects of this variant on the resulting mRNA or protein product determined. Exon 6 deletions have been previously reported in the literature in individuals or families with Lynch Syndrome (Gille 2002, Hendricks 2003, Overbeek 2007, van der Klift 2005); in the studies by Hendricks (2003) and Overbeek (2007), tumour analysis showed loss of MSH2 expression and microsatellite instability, respectively. The variant was also identified in the following databases: GeneInsight-COGR, InSiGHT (classified as pathogenic) ClinVar (submitted by InSiGHT), Clinvitae (submitted by ClinVar), UMD (9x with a “causal” classification), and the “Mismatch Repair Genes Variant Database”. The deletion of exon 6 is predicted to result in a truncated or absent protein and loss of function. Loss of function variants of the MSH2 gene are an established mechanism of disease in Lynch syndrome and this is the type of variant expected to cause the disorder. In summary, based on the above information, this variant meets our laboratory’s criteria to be classified as pathogenic.

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