ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.2275+1G>A (rs1554294393)

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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 RCV000573476 SCV000663525 likely pathogenic Hereditary cancer-predisposing syndrome 2016-08-25 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations at the canonical donor/acceptor sites (+/- 1, 2) without other strong (b-level) evidence supporting pathogenicity
GeneDx RCV000520083 SCV000617062 pathogenic not provided 2017-04-04 criteria provided, single submitter clinical testing This variant is denoted PMS2 c.2275+1G>A or IVS13+1G>A and consists of a G>A nucleotide substitution at the +1 position of intron 13 of the PMS2 gene. This 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-mediated mRNA decay or to an abnormal protein product. This variant has been reported in at least two individuals with Lynch-associated personal and family histories where tumor testing in both individuals reported microsatellite instability and immunohistochemistry showing the presence of MLH1 and the absence of PMS2 (van der Klift 2016). Based on the current evidence, we consider this variant to be pathogenic.

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