ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.2634+5G>T (rs267608017)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000076522 SCV000260295 likely pathogenic Lynch syndrome 2015-08-28 criteria provided, single submitter clinical testing This sequence change falls in intron 15 of the MSH2 mRNA. It does not directly change the encoded amino acid sequence of the MSH2 protein. This variant is not present in population databases and has been reported in an individual with Lynch syndrome (PMID: 18561205). ClinVar also contains an entry for this variant (RCV000076522). Experimental studies based on ex vivo splicing assay demonstrated that this intronic change likely results in exon 15 skipping (PMID: 18561205). A different variant affecting this nucleotide (c.2634+5G>C) has been reported to segregate with colorectal cancer in five affected individuals within a single family (PMID: 18033691). The tumor of the proband in this family was MSI-H and immunohistochemistry indicated a loss of MSH2 protein. Furthermore, cDNA analysis revealed MSH2 exon 15 skipping. This suggests that this nucleotide may be crucial for normal mRNA splicing. For these reasons, this variant has been classified as Likely Pathogenic.

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