Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000425644 | SCV000527261 | likely benign | not specified | 2016-05-02 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000425644 | SCV000918038 | uncertain significance | not specified | 2018-10-08 | criteria provided, single submitter | clinical testing | Variant summary: PMS2 c.353+3G>A alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4.3e-06 in 230064 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.353+3G>A in individuals affected with Lynch Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance. |
Invitae | RCV001211500 | SCV001383041 | likely benign | Hereditary nonpolyposis colorectal neoplasms | 2024-01-07 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV002258890 | SCV002530328 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-04-23 | criteria provided, single submitter | curation | |
Ambry Genetics | RCV002258890 | SCV002614059 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-10 | criteria provided, single submitter | clinical testing | The c.353+3G>A intronic variant results from a G to A substitution 3 nucleotides after coding exon 4 in the PMS2 gene. This nucleotide position is poorly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing; however, direct evidence is insufficient at this time (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
All of Us Research Program, |
RCV004000433 | SCV004826363 | uncertain significance | Lynch syndrome | 2023-08-15 | criteria provided, single submitter | clinical testing | This variant causes a G to A nucleotide substitution at the +3 position of intron 4 of the PMS2 gene. 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 been identified in 1/234666 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. |