Submissions for variant NM_000251.3(MSH2):c.1077-3C>T

gnomAD frequency: 0.00001  dbSNP: rs758182607

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000221368	SCV000276806	likely benign	Hereditary cancer-predisposing syndrome	2019-03-19	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
GeneDx	RCV000235545	SCV000293897	uncertain significance	not provided	2016-02-23	criteria provided, single submitter	clinical testing	This variant is denoted MSH2 c.1077-3C>T or IVS6-3C>T and consists of a C>T nucleotide substitution at the -3 position of intron 6 of the MSH2 gene. Multiple in silico models predict this variant to weaken the nearby natural acceptor site, and to possibly cause abnormal gene splicing; however, in the absence of RNA or functional studies, the actual effect of this variant is unknown. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. MSH2 c.1077-3C>T was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. The cytosine (C) nucleotide that is altered is not conserved across species. Based on currently available information, it is unclear whether MSH2 c.1077-3C>T is pathogenic or benign.
Invitae	RCV000629733	SCV000750689	likely benign	Hereditary nonpolyposis colorectal neoplasms	2023-12-09	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000221368	SCV000903425	likely benign	Hereditary cancer-predisposing syndrome	2015-04-29	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV002267962	SCV002552217	uncertain significance	not specified	2023-08-15	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003150127	SCV003838300	uncertain significance	Breast and/or ovarian cancer	2022-05-17	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV003997988	SCV004815798	likely benign	Lynch syndrome	2023-12-15	criteria provided, single submitter	clinical testing