Total submissions: 5
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. |