ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.24-12_107delinsAAAT (rs1554306445)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000076856 SCV000108350 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation resulting in a stop codon (also interrupts canonical acceptor splice site)
GeneDx RCV000482984 SCV000568133 pathogenic not provided 2016-11-21 criteria provided, single submitter clinical testing This variant is denoted PMS2 c.24-12_107delinsAAAT and consists of a deletion of 96 nucleotides and insertion of four nucleotides, which results in the destruction of the natural splice acceptor site for intron 1. The normal sequence, with the bases that are deleted in braces and inserted in brackets, is taac[del96][AAAT]CACT, where the capital letters are exonic and lowercase are intronic. This variant, which has been identified in individuals with Lynch syndrome, was shown by an RNA-based study to result in out of frame skipping of exon 2 and is predicted to result in a frameshift (van der Klift 2010, Ten Broeke 2015, Suerink 2015). We consider this variant to be pathogenic.
Invitae RCV000629965 SCV000750921 pathogenic Hereditary nonpolyposis colon cancer 2019-09-04 criteria provided, single submitter clinical testing This variant is a deletion of the genomic region encompassing part of exon 2, including the intron 1 - exon 2 boundary of the PMS2 gene (c.24-12_107delinsAAAT). It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant has been observed in individuals affected with Lynch syndrome and Lynch syndrome-associated cancers in the literature (PMID: 20186688). ClinVar contains an entry for this variant (Variation ID: 91341). Experimental studies have shown that this variant results in out-of-frame skipping of exon 2 (PMID: 20186688). Loss-of-function variants in PMS2 are known to be pathogenic (PMID: 21376568, 24362816). For these reasons, this variant has been classified as Pathogenic.

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