Submissions for variant NM_000251.3(MSH2):c.212-2A>G

dbSNP: rs267607917

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT)	RCV000076395	SCV000107431	likely pathogenic	Lynch syndrome	2019-06-21	reviewed by expert panel	curation	Interrupts canonical donor splice site
Ambry Genetics	RCV002415565	SCV002729924	likely pathogenic	Hereditary cancer-predisposing syndrome	2020-04-07	criteria provided, single submitter	clinical testing	The c.212-2A>G intronic variant results from an A to G substitution two nucleotides upstream from coding exon 2 in the MSH2 gene. This variant (designated aagGAG>aggGAG) was identified in a family meeting Amsterdam criteria (Wijnen J et al. Am. J. Hum. Genet. 1997 Aug;61:329-35) and in a family with early onset endometrial cancer (Jóri B et al. Oncotarget 2015 Dec;6:41108-22). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to create a new alternate splice acceptor site; however, direct evidence is unavailable. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic.
Myriad Genetics, Inc.	RCV003452891	SCV004186685	likely pathogenic	Lynch syndrome 1	2023-07-26	criteria provided, single submitter	clinical testing	This variant is considered likely pathogenic. This variant occurs within a consensus splice junction and is predicted to result in abnormal mRNA splicing of either an out-of-frame exon or an in-frame exon necessary for protein stability and/or normal function.
Clinical Genetics, Academic Medical Center	RCV001699196	SCV001924222	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001699196	SCV001954468	pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001699196	SCV001965368	pathogenic	not provided		no assertion criteria provided	clinical testing