Submissions for variant NM_000535.7(PMS2):c.803+2T>G

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002419292	SCV002680031	pathogenic	Hereditary cancer-predisposing syndrome	2024-07-17	criteria provided, single submitter	clinical testing	The c.803+2T>G intronic pathogenic mutation results from a T to G substitution two nucleotides after coding exon 7 in the PMS2 gene. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This nucleotide position is highly conserved in available vertebrate species. This variant was reported as homozygous in an individual with features consistent with CMMRD, and as heterozygous in an individual with features consistent with HNPCC (Ambry internal data). In addition to the clinical data presented, 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 a disease-causing mutation.
Myriad Genetics, Inc.	RCV003454209	SCV004187651	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.