Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000587489 | SCV000697304 | likely pathogenic | Lynch syndrome | 2017-08-21 | criteria provided, single submitter | clinical testing | Variant summary: The c.1634_1635delCT (p.Ser545Phefs) variant in PMS2 gene is a frameshift change that results in the loss of the ~303 amino acids of PMS2 protein (~35%). This change is predicted to cause loss of normal protein function through protein truncation or nonsense-mediated mRNA decay. The variant is absent from the large control population datasets of ExAC and gnomAD (120412 and 245704 chrs tested, respectively). The c.1634_1635delCT has not, to our knowledge, been reported in affected individuals via published reports or cited by reputable databases/clinical laboratories. Other truncated variants, such as c. 1768delA and c. c.1874delT, have been reported in association with LS. Taking together, the variant was classified as Likely Pathogenic. |
| Invitae | RCV003758870 | SCV004380738 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2023-09-30 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ser545Phefs*16) in the PMS2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PMS2 are known to be pathogenic (PMID: 21376568, 24362816). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PMS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 496032). For these reasons, this variant has been classified as Pathogenic. |