Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000076818 | SCV000108272 | likely pathogenic | Lynch syndrome | 2019-06-21 | reviewed by expert panel | curation | Interrupts canonical donor splice site |
Center for Genomic Medicine, |
RCV003320559 | SCV004025140 | likely pathogenic | not provided | 2023-08-15 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV000076818 | SCV004843102 | likely pathogenic | Lynch syndrome | 2023-11-27 | criteria provided, single submitter | clinical testing | The c.164-2A>G variant in the PMS2 gene is located at the canonical splice site of intron 2 and is predicted to inflict acceptor loss (SpliceAI delta score: 0.99), resulting in aberrant splicing and disrupted protein product. The variant has been reported in an individual with colorectal cancer, and experimental RNA analysis from patient's lymphocytes showed aberrant transcripts and negative functional impact (PMID: 23709753). Loss-of-function variants in PMS2 are known to be pathogenic (PMID: 28514183, 25512458, 35223509). The variant is reported in ClinVar as likely pathogenic (ID: 91308) and reviewed by the expert panel. The variant is absent in the general population database (gnomAD). Therefore, the c.164-2A>G variant of PMS2 has been classified as likely pathogenic. |