Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000221391 | SCV000274496 | likely benign | Hereditary cancer-predisposing syndrome | 2018-08-21 | criteria provided, single submitter | clinical testing | In silico models in agreement (benign);Other strong data supporting benign classification |
| Gene |
RCV000521141 | SCV000616825 | uncertain significance | not provided | 2017-11-03 | criteria provided, single submitter | clinical testing | This variant is denoted PMS2 c.1354G>A at the cDNA level, p.Gly452Ser (G452S) at the protein level, and results in the change of a Glycine to a Serine (GGT>AGT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. PMS2 Gly452Ser was not observed at a significant allele frequency in large population cohorts (Lek 2016). Since Glycine and Serine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. PMS2 Gly452Ser occurs at a position that is not conserved and is not located in a known functional domain. In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available evidence, it is unclear whether PMS2 Gly452Ser is pathogenic or benign. We consider it to be a variant of uncertain significance. |
| Invitae | RCV000629994 | SCV000750950 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2019-10-30 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with serine at codon 452 of the PMS2 protein (p.Gly452Ser). The glycine residue is weakly conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs569947936, ExAC 0.02%). This variant has not been reported in the literature in individuals with PMS2-related disease. ClinVar contains an entry for this variant (Variation ID: 230823). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 | RCV000221391 | SCV000903598 | likely benign | Hereditary cancer-predisposing syndrome | 2017-01-03 | criteria provided, single submitter | clinical testing |