ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1144+4A>G

dbSNP: rs1554298642
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Total submissions: 4
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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, LLC DBA Color Health 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.

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