Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000567942 | SCV000663464 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-09-29 | criteria provided, single submitter | clinical testing | The c.1144+4A>G intronic variant results from an A to G substitution 4 nucleotides after coding exon 10 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 not have any significant effect on splicing. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Invitae | RCV001345587 | SCV001539717 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2022-11-09 | criteria provided, single submitter | clinical testing | 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. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown this variant is associated with skipping of exon 10, but one or more of the resulting mRNA isoform(s) may be naturally occurring (Invitae). ClinVar contains an entry for this variant (Variation ID: 480309). 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 falls in intron 10 of the PMS2 gene. It does not directly change the encoded amino acid sequence of the PMS2 protein. It affects a nucleotide within the consensus splice site. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003478216 | SCV004218938 | uncertain significance | not provided | 2023-08-02 | criteria provided, single submitter | clinical testing | This variant has not been reported in the published literature. It also has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Analysis of this variant using software algorithms for the prediction of the effect of nucleotide changes on PMS2 mRNA splicing yielded inconclusive findings . Based on the available information, we are unable to determine the clinical significance of this variant. |
Color Diagnostics, |
RCV000567942 | SCV004359633 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-20 | criteria provided, single submitter | clinical testing | This variant causes an A to G nucleotide substitution at the +4 position of intron 10 of the PMS2 gene. Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with PMS2-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |