Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000693535 | SCV000821408 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2022-11-08 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu491Alafs*9) 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). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 572207). 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). |
Myriad Genetics, |
RCV003453455 | SCV004188691 | pathogenic | Lynch syndrome 4 | 2023-09-20 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |
Color Diagnostics, |
RCV003584714 | SCV004359605 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-07-21 | criteria provided, single submitter | clinical testing | This variant deletes 14 nucleotides in exon 11 of the PMS2 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, this variant has not been reported in individuals affected with PMS2-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of PMS2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. |