ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.790_803+5del

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Myriad Genetics, Inc. RCV003452398 SCV004187659 likely pathogenic Lynch syndrome 4 2023-09-19 criteria provided, single submitter clinical testing This variant is considered likely pathogenic. This variant occurs within a consensus splice junction and is predicted to result in abnormal mRNA splicing of either an out-of-frame exon or an in-frame exon necessary for protein stability and/or normal function.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV003477091 SCV004219027 pathogenic not provided 2022-10-20 criteria provided, single submitter clinical testing This frameshift variant alters the translational reading frame of the PMS2 mRNA and causes the premature termination of PMS2 protein synthesis. The variant has not been reported in individuals with PMS2-related diseases in the published literature. It also has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). Based on the available information, this variant is classified as pathogenic.
Ambry Genetics RCV004654229 SCV005148289 likely pathogenic Hereditary cancer-predisposing syndrome 2024-06-18 criteria provided, single submitter clinical testing The c.790_803+5del19 variant results from a deletion of 19 nucleotides between positions c.790 and c.803+5 and involves the canonical splice donor site after coding exon 7 of the PMS2 gene. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). The canonical splice donor site is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site; however, direct evidence is insufficient at this time (Ambry internal data). Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic.

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