Submissions for variant NM_000251.3(MSH2):c.2006-6T>C

gnomAD frequency: 0.08349  dbSNP: rs2303428

Total submissions: 24

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT)	RCV000030247	SCV000107378	no known pathogenicity	Lynch syndrome	2013-09-05	reviewed by expert panel	research	MAF >1%
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000030247	SCV000052914	benign	Lynch syndrome	2011-08-18	criteria provided, single submitter	curation	Converted during submission to Benign.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000035359	SCV000059007	benign	not specified	2010-10-07	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000035359	SCV000110274	benign	not specified	2014-06-24	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000035359	SCV000303161	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000144621	SCV000430931	benign	Lynch syndrome 1	2018-03-06	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Color Diagnostics, LLC DBA Color Health	RCV000448700	SCV000537344	benign	Hereditary cancer-predisposing syndrome	2022-01-02	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001668140	SCV000604256	benign	not provided	2023-11-17	criteria provided, single submitter	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000144621	SCV000744279	benign	Lynch syndrome 1	2015-09-21	criteria provided, single submitter	clinical testing
Invitae	RCV000860335	SCV001000360	benign	Hereditary nonpolyposis colorectal neoplasms	2024-02-01	criteria provided, single submitter	clinical testing
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV001196507	SCV001367115	benign	Mismatch repair cancer syndrome 1	2019-11-12	criteria provided, single submitter	clinical testing	This variant was classified as: Benign. The following ACMG criteria were applied in classifying this variant: BA1.
Institute of Human Genetics, University of Leipzig Medical Center	RCV000144621	SCV001440728	benign	Lynch syndrome 1	2019-01-01	criteria provided, single submitter	clinical testing
GeneDx	RCV001668140	SCV001884197	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 27629256, 7797014, 22933969, 24689082, 20708344, 18561205, 22283331, 21671081, 20438357)
Sema4, Sema4	RCV000448700	SCV002534439	benign	Hereditary cancer-predisposing syndrome	2020-02-04	criteria provided, single submitter	curation
Ambry Genetics	RCV000448700	SCV002719482	benign	Hereditary cancer-predisposing syndrome	2014-11-18	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: 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.
Fulgent Genetics, Fulgent Genetics	RCV002496465	SCV002805712	benign	Lynch syndrome 1; Muir-Torré syndrome; Mismatch repair cancer syndrome 2	2021-11-10	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000144621	SCV004015933	benign	Lynch syndrome 1	2023-07-07	criteria provided, single submitter	clinical testing
Pathway Genomics	RCV000144621	SCV000189948	benign	Lynch syndrome 1	2014-07-24	no assertion criteria provided	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000035359	SCV000257164	benign	not specified		no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000035359	SCV000592527	benign	not specified		no assertion criteria provided	clinical testing	The c.2006-6T>C variant is not expected to have clinical significance because it is a common variant in the general population with an average heterozygosity of 36.8% (dbSNP#: rs2303428).
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000144621	SCV000734203	benign	Lynch syndrome 1		no assertion criteria provided	clinical testing
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000035359	SCV001905802	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000035359	SCV001920182	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000035359	SCV001951018	benign	not specified		no assertion criteria provided	clinical testing