ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.2635-1G>T (rs267608020)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000076525 SCV000107556 likely pathogenic Lynch syndrome 2019-06-21 reviewed by expert panel curation Interrupts canonical acceptor splice site
Invitae RCV000629741 SCV000750697 uncertain significance Hereditary nonpolyposis colon cancer 2017-11-02 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in the last intron (intron 15) of the MSH2 gene. While this is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual suspected of being affected with Lynch syndrome (PMID: 15849733). ClinVar contains an entry for this variant (Variation ID: 91023). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). 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.

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