Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000466795 | SCV000552036 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2023-06-29 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 411069). This variant has not been reported in the literature in individuals affected with PMS2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Lys450*) 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). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003114589 | SCV003800807 | likely pathogenic | Hereditary nonpolyposis colon cancer | 2023-01-17 | criteria provided, single submitter | clinical testing | Variant summary: PMS2 c.1348A>T (p.Lys450X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251476 control chromosomes. To our knowledge, no occurrence of c.1348A>T in individuals affected with Hereditary Nonpolyposis Colorectal Cancer and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Ambry Genetics | RCV003168843 | SCV003887913 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-12-02 | criteria provided, single submitter | clinical testing | The p.K450* pathogenic mutation (also known as c.1348A>T), located in coding exon 11 of the PMS2 gene, results from an A to T substitution at nucleotide position 1348. This changes the amino acid from a lysine to a stop codon within coding exon 11. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |