Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV000582218 | SCV000691083 | likely benign | Hereditary cancer-predisposing syndrome | 2016-12-13 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000582218 | SCV003859093 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-11-29 | criteria provided, single submitter | clinical testing | The c.538-12T>G intronic variant results from a T to G substitution 12 nucleotides upstream from coding exon 6 in the PMS2 gene. This nucleotide position is not well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site. RNA studies have demonstrated that this alteration results in an incomplete splice defect involving exons excluded from naturally occurring transcripts; the clinical impact of this abnormal splicing is unknown at this time (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Invitae | RCV003594000 | SCV004267140 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2023-10-04 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 5 of the PMS2 gene. It does not directly change the encoded amino acid sequence of the PMS2 protein. 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. ClinVar contains an entry for this variant (Variation ID: 492282). Studies have shown this variant is associated with partial deletion of exon 6, but one or more of the resulting mRNA isoform(s) may be naturally occurring (Invitae). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |