ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.24-4C>G (rs2345056)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Health, Inc RCV000584647 SCV000691059 likely benign Hereditary cancer-predisposing syndrome 2017-11-06 criteria provided, single submitter clinical testing
Invitae RCV000699503 SCV000828216 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2020-09-02 criteria provided, single submitter clinical testing This sequence change falls in intron 1 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 (ExAC no frequency). This variant has not been reported in the literature in individuals with PMS2-related disease. ClinVar contains an entry for this variant (Variation ID: 492274). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
Ambry Genetics RCV000584647 SCV001176428 uncertain significance Hereditary cancer-predisposing syndrome 2020-06-02 criteria provided, single submitter clinical testing The c.24-4C>G intronic variant results from a C to G substitution 4 nucleotides upstream from coding exon 2 in the PMS2 gene. This nucleotide position is poorly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to weaken the efficiency of the native splice acceptor site; however, direct evidence is insufficient at this time (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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