Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000460430 | SCV000552047 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2023-10-04 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 218 of the PMS2 protein (p.Gly218Asp). This variant is present in population databases (rs368043334, gnomAD 0.006%). 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: 135071). 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. 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. |
Color Diagnostics, |
RCV000580059 | SCV000686224 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-11-03 | criteria provided, single submitter | clinical testing | This missense variant replaces glycine with aspartic acid at codon 218 of the PMS2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 3/251490 chromosomes 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. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000985912 | SCV001134605 | uncertain significance | not provided | 2019-07-09 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000580059 | SCV001187564 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-14 | criteria provided, single submitter | clinical testing | The p.G218D variant (also known as c.653G>A), located in coding exon 6 of the PMS2 gene, results from a G to A substitution at nucleotide position 653. The glycine at codon 218 is replaced by aspartic acid, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Fulgent Genetics, |
RCV002483227 | SCV002776287 | uncertain significance | Lynch syndrome 4; Mismatch repair cancer syndrome 4 | 2022-03-17 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000985912 | SCV004167918 | uncertain significance | not provided | 2023-10-11 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 11574484, 24728327) |
All of Us Research Program, |
RCV003997357 | SCV004839942 | uncertain significance | Lynch syndrome | 2023-09-18 | criteria provided, single submitter | clinical testing | This missense variant replaces glycine with aspartic acid at codon 218 of the PMS2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 3/251490 chromosomes 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. |
ITMI | RCV000121859 | SCV000086061 | not provided | not specified | 2013-09-19 | no assertion provided | reference population |