ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.537+1del (rs1064793868)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000485795 SCV000567235 pathogenic not provided 2015-07-08 criteria provided, single submitter clinical testing This pathogenic variant is denoted PMS2 c.537+1delG or IVS5+1delG and consists of a single nucleotide deletion at the +1 position of intron 5 of the PMS2 gene. The variant destroys a canonical splice donor site and is predicted to cause abnormal gene splicing, leading to either an abnormal message that is subject to nonsense-medicated mRNA decay or to an abnormal protein product. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. Based on the current evidence, we consider this variant to be pathogenic.
Invitae RCV001223326 SCV001395468 likely pathogenic Hereditary nonpolyposis colorectal neoplasms 2019-05-24 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 5 of the PMS2 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). Disruption of this splice site has been observed in a family with clinical features of Lynch syndrome (PMID: 20587412). ClinVar contains an entry for this variant (Variation ID: 419435). 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). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
True Health Diagnostics RCV000758169 SCV000886701 pathogenic Hereditary cancer-predisposing syndrome 2018-10-03 no assertion criteria provided clinical testing

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