Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000586329 | SCV000697326 | uncertain significance | not provided | 2016-11-04 | criteria provided, single submitter | clinical testing | Variant summary: The PMS2 c.2092G>A (p.Val698Met) variant causes a missense change involving a conserved nucleotide with 2/3 in silico tools (SNPs&GO and Mutation Taster not captured here due to low reliability index and p-value, respectively) predict a "damaging" outcome, although these predictions have yet to be functionally assessed. The variant of interest was not observed in controls (ExAC, 1000 Gs, or ESP), and has not been reported, to our knowledge, in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories. Therefore, until additional information becomes available (ie, clinical and functional studies), the variant of interest has been classified as a "Variant of Uncertain Significance (VUS)." |
| Ambry Genetics | RCV002420563 | SCV002725793 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-16 | criteria provided, single submitter | clinical testing | The p.V698M variant (also known as c.2092G>A), located in coding exon 12 of the PMS2 gene, results from a G to A substitution at nucleotide position 2092. The valine at codon 698 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |
| Color Diagnostics, |
RCV002420563 | SCV004359556 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-07-12 | criteria provided, single submitter | clinical testing | This missense variant replaces valine with methionine at codon 698 of the PMS2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. 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). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |