ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.2006-2A>G (rs267607991)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000076349 SCV000107375 likely pathogenic Lynch syndrome 2019-06-21 reviewed by expert panel curation Interrupts canonical donor splice site
Color RCV000774579 SCV000908323 pathogenic Hereditary cancer-predisposing syndrome 2019-02-28 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000076349 SCV000917706 pathogenic Lynch syndrome 2018-11-08 criteria provided, single submitter clinical testing Variant summary: MSH2 c.2006-2A>G is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Five predict the variant abolishes a 3 acceptor site. These predictions are supported by a functional study, Ding_2007, which indicates the variant causes exon 13 skipping. The variant was absent in 246132 control chromosomes (gnomAD). c.2006-2A>G has been reported in the literature in individuals affected with Lynch Syndrome including a de novo occurrence (Ding_2007, Morak_2017, Parc_2003). These data indicate that the variant may be associated with disease. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.

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