ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.163+4A>G (rs864622749)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000205498 SCV000262291 uncertain significance Hereditary nonpolyposis colon cancer 2019-10-30 criteria provided, single submitter clinical testing This sequence change falls in intron 2 of the PMS2 gene. It does not directly change the encoded amino acid sequence of the PMS2 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the literature in an individual with suspected Lynch syndrome (PMID: 25980754). ClinVar contains an entry for this variant (Variation ID: 221108). Nucleotide substitutions within the consensus splice site are relatively common causes of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of nucleotide changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this is a rare intronic change with uncertain impact on splicing. While it is absent from the population and reported in an affected individual, the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Counsyl RCV000409621 SCV000488510 uncertain significance Hereditary nonpolyposis colorectal cancer type 4 2016-04-13 criteria provided, single submitter clinical testing
Color RCV000580174 SCV000686147 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-26 criteria provided, single submitter clinical testing

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