ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.2005+1G>A (rs267607986)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000076337 SCV000107361 likely pathogenic Lynch syndrome 2019-06-21 reviewed by expert panel curation Interrupts canonical donor splice site
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000078422 SCV000110273 pathogenic not provided 2017-09-28 criteria provided, single submitter clinical testing
Ambry Genetics RCV001014038 SCV001174697 pathogenic Hereditary cancer-predisposing syndrome 2019-06-13 criteria provided, single submitter clinical testing Alterations at the canonical donor/acceptor sites (+/- 1, 2) without other strong (b-level) evidence supporting pathogenicity;Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation;In silico models in agreement (deleterious) and/or completely conserved position in appropriate species;Rarity in general population databases (dbsnp, esp, 1000 genomes)
Invitae RCV001068056 SCV001233145 likely pathogenic Hereditary nonpolyposis colon cancer 2019-10-07 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 12 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 individuals affected with Lynch syndrome (PMID: 16142001, 21642682). ClinVar contains an entry for this variant (Variation ID: 90835). 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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