Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000485795 | SCV000567235 | pathogenic | not provided | 2015-07-08 | criteria provided, single submitter | clinical testing | This pathogenic variant is denoted PMS2 c.537+1delG or IVS5+1delG and consists of a single nucleotide deletion at the +1 position of intron 5 of the PMS2 gene. The variant destroys a canonical splice donor site and is predicted to cause abnormal gene splicing, leading to either an abnormal message that is subject to nonsense-medicated mRNA decay or to an abnormal protein product. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. Based on the current evidence, we consider this variant to be pathogenic. |
Invitae | RCV001223326 | SCV001395468 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2023-10-14 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu180Serfs*21) in the PMS2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PMS2 are known to be pathogenic (PMID: 21376568, 24362816). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PMS2-related conditions. This variant is also known as c.537+1del. ClinVar contains an entry for this variant (Variation ID: 419435). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Ambry Genetics | RCV000758169 | SCV002646454 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-12-23 | criteria provided, single submitter | clinical testing | The c.537+1delG intronic pathogenic mutation, located in intron 5 of the PMS2 gene, results from a deletion of one nucleotide within intron 5 of the PMS2 gene. This alteration has been observed in an individual diagnosed with colorectal cancer exhibiting loss of PMS2 protein by immunohistochemistry in their 40s (Ambry internal data). 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 and will result in the creation or strengthening of a novel 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 a disease-causing mutation. |
Fulgent Genetics, |
RCV002506164 | SCV002813821 | likely pathogenic | Lynch syndrome 4; Mismatch repair cancer syndrome 4 | 2021-11-15 | criteria provided, single submitter | clinical testing | |
Myriad Genetics, |
RCV003449191 | SCV004187642 | 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 | RCV003449191 | SCV004205406 | likely pathogenic | Lynch syndrome 4 | 2023-10-06 | criteria provided, single submitter | clinical testing | |
True Health Diagnostics | RCV000758169 | SCV000886701 | pathogenic | Hereditary cancer-predisposing syndrome | 2018-10-03 | no assertion criteria provided | clinical testing |