Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001284681 | SCV001470609 | likely pathogenic | not provided | 2019-12-20 | criteria provided, single submitter | clinical testing | The variant disrupts a canonical splice site, and is therefore predicted to result in the loss of a functional protein. Not found in the total gnomAD dataset, and the data is high quality. |
| Ambry Genetics | RCV002375329 | SCV002688040 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2019-08-29 | criteria provided, single submitter | clinical testing | The c.903+1G>A intronic variant results from a G to A substitution one nucleotide after coding exon 8 of the PMS2 gene. This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice donor site; however, direct evidence is unavailable. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic. |
| Labcorp Genetics |
RCV002537934 | SCV003327011 | likely pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2022-10-25 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 993233). This variant has not been reported in the literature in individuals affected with PMS2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 8 of the PMS2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PMS2 are known to be pathogenic (PMID: 21376568, 24362816). |
| Gene |
RCV001284681 | SCV003930933 | likely pathogenic | not provided | 2022-11-03 | criteria provided, single submitter | clinical testing | Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Observed in an individual with a personal history consistent with pathogenic variants in this gene in the published literature (Shuen et al., 2019); This variant is associated with the following publications: (PMID: 30608896) |
| Myriad Genetics, |
RCV003449837 | SCV004187634 | likely pathogenic | Lynch syndrome 4 | 2023-09-19 | criteria provided, single submitter | clinical testing | This variant is considered likely pathogenic. This variant occurs within a consensus splice junction and is predicted to result in abnormal mRNA splicing of either an out-of-frame exon or an in-frame exon necessary for protein stability and/or normal function. |
| Baylor Genetics | RCV003449837 | SCV004203429 | likely pathogenic | Lynch syndrome 4 | 2020-12-29 | criteria provided, single submitter | clinical testing | |
| Department of Pathology and Laboratory Medicine, |
RCV001284681 | SCV001549121 | uncertain significance | not provided | no assertion criteria provided | clinical testing |