ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.2635-3_2805del

dbSNP: rs2104459054
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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 RCV001357881 SCV001553475 pathogenic not provided no assertion criteria provided clinical testing The c.2635-?_2805+?del deletion variant (chr2.hg19.g.47709894 -?_ 47709960+?del) results in a deletion of exon 16, 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. In-silico prediction software suggests that this variant may result in an in-frame deletion of exon 16 with the following affect: p.Gln879_Thr934delinsLysIleProValMetGlu. Additional study would be necessary to confirm this prediction. The variant was identified in 3 of 2546 proband chromosomes (frequency: 0.001) from individuals or families with Lynch syndrome (Buchanan 2014, De Lellis 2013, van der Klift 2005). The variant was also identified in HGMD, the “Mismatch Repair Genes Variant Database”, “InSiGHT Colon Cancer Database” “Zhejiang Colon Cancer Database”, and ClinVar database (submitted by InSiGHT with a classification of “pathogenic”). A study by Buchanan (2014) demonstrated a loss of MSH2 expression by IHC in a tumour with a deletion of exon 16. In addition, in the “InSiGHT Colon Cancer Database” the variant was identified in four tumours showing a loss of MSH2 expression by IHC. 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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