Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV001185631 | SCV001351883 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-01-15 | criteria provided, single submitter | clinical testing | This variant deletes 2 nucleotides in exon 3 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. 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. |
| Labcorp Genetics |
RCV001389865 | SCV001591386 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2020-01-20 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Leu58*) in the PMS2 gene. It is expected to result in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in PMS2 are known to be pathogenic (PMID: 21376568, 24362816). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with PMS2-related conditions. This variant is not present in population databases (ExAC no frequency). |
| Myriad Genetics, |
RCV004590162 | SCV005083705 | pathogenic | Lynch syndrome 4 | 2024-06-25 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation. |
| Ambry Genetics | RCV001185631 | SCV005472538 | pathogenic | Hereditary cancer-predisposing syndrome | 2024-10-15 | criteria provided, single submitter | clinical testing | The c.172_173delCT pathogenic mutation, located in coding exon 3 of the PMS2 gene, results from a deletion of two nucleotides at nucleotide positions 172 to 173, causing a translational frameshift with a predicted alternate stop codon (p.L58*). 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. |