ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.646-2A>G (rs587779169)

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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) RCV000076665 SCV000107707 likely pathogenic Lynch syndrome 2019-06-21 reviewed by expert panel curation Interrupts canonical donor splice site
Invitae RCV000817666 SCV000958243 likely pathogenic Hereditary nonpolyposis colon cancer 2018-12-22 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 3 of the MSH2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with endometrial cancer (PMID: 26517685), and several individuals affected with Lynch syndrome (PMID: 12624141, 21642682). This variant is also known as IVS3-2A>G in the literature. ClinVar contains an entry for this variant (Variation ID: 91161). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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