Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000525126 | SCV000625587 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2024-11-27 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 718 of the PMS2 protein (p.Leu718Phe). The frequency data for this variant in the population databases (gnomAD) is considered unreliable due to the presence of homologous sequence, such as pseudogenes or paralogs, in the genome. 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: 455686). Invitae Evidence Modeling incorporating data from in vitro experimental studies (internal data) indicates that this missense variant is not expected to disrupt PMS2 function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV002431525 | SCV002728063 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-10-13 | criteria provided, single submitter | clinical testing | The p.L718F variant (also known as c.2152C>T), located in coding exon 12 of the PMS2 gene, results from a C to T substitution at nucleotide position 2152. The leucine at codon 718 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Baylor Genetics | RCV004568720 | SCV005056400 | uncertain significance | Lynch syndrome 4 | 2024-03-10 | criteria provided, single submitter | clinical testing | |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV005000124 | SCV005625902 | uncertain significance | not provided | 2024-10-25 | criteria provided, single submitter | clinical testing | The PMS2 c.2152C>T (p.Leu718Phe) variant has not been reported in individuals with PMS2-related conditions in the published literature. The frequency of this variant in the general population, 0.000032 (1/31138 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is deleterious or benign. Based on the available information, we are unable to determine the clinical significance of this variant. |