ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.2007-2A>C (rs587782336)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131264 SCV000186230 likely pathogenic Hereditary cancer-predisposing syndrome 2017-02-08 criteria provided, single submitter clinical testing Alterations at the canonical donor/acceptor sites (+/- 1, 2) without other strong (b-level) evidence supporting pathogenicity
Invitae RCV000818298 SCV000958901 pathogenic Hereditary nonpolyposis colon cancer 2019-09-24 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 11 of the PMS2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. The frequency data for this variant in the population databases (ExAC) is considered unreliable due to the presence of homologous sequence, such as pseudogenes or paralogs, in the genome. Disruption of this splice site has been observed in an individual who underwent hereditary cancer testing (PMID: 24763289) and in two individuals affected with constitutional mismatch repair deficiency (CMMRD) syndrome in the homozygous state (PMID: 26318770). ClinVar contains an entry for this variant (Variation ID: 142251). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and 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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