Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000230352 | SCV000285160 | likely pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2021-11-19 | 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. ClinVar contains an entry for this variant (Variation ID: 237930). Disruption of this splice site has been observed in individual(s) with clinical features of Lynch syndrome (Invitae). This variant is present in population databases (no rsID available, gnomAD 0.003%). 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). |
Ambry Genetics | RCV002372260 | SCV002686337 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2022-05-16 | criteria provided, single submitter | clinical testing | The c.903+2T>C intronic variant results from a T to C substitution two nucleotides after coding exon 8 in the PMS2 gene. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site; however, direct evidence is insufficient at this time (Ambry internal data). 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. |
Myriad Genetics, |
RCV003454707 | SCV004187623 | 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. |