Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000780625 | SCV000918053 | uncertain significance | not specified | 2018-01-08 | criteria provided, single submitter | clinical testing | Variant summary: The PMS2 c.1631A>T (p.Asp544Val) variant involves the alteration of a non-conserved nucleotide and 3/4 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). However, these predictions have yet to be functionally assessed. This variant is absent in 245568 control chromosomes (gnomAD). The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a "Variant of Uncertain Significance (VUS)," until additional information becomes available. |
| Invitae | RCV002536866 | SCV003008623 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2023-06-27 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with PMS2-related conditions. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PMS2 protein function. ClinVar contains an entry for this variant (Variation ID: 632950). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 544 of the PMS2 protein (p.Asp544Val). |