ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.640_645+1del

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
KCCC/NGS Laboratory, Kuwait Cancer Control Center RCV003315486 SCV004015217 likely pathogenic Lynch syndrome 1 2023-07-07 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 3 of the MSH2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MSH2-related disease. ClinVar does not contain an entry for this variant. However, ClinVar contains an entry for another variant that affects the same splicesite (Variation ID: 231167) and it is described as likely pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). Therefore, this variant has been classified as Likely Pathogenic.

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