Submissions for variant NM_000251.3(MSH2):c.1661+12G>A

gnomAD frequency: 0.40290  dbSNP: rs3732183

Total submissions: 20

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT)	RCV000030241	SCV000107233	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	RCV000030241	SCV000052908	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	RCV000035358	SCV000059006	benign	not specified	2012-12-03	criteria provided, single submitter	clinical testing	1661+12G>A in intron 10 of MSH2: This variant is not expected to have clinical s ignificance because it is not located within the conserved +/- 1, 2 invariant re gion. It has been identified in >50% of African American chromosomes from a broa d population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu /EVS/; rs3732183). 1661+12G>A in intron 10 of MSH2 (rs3732183; allele frequency = >50%, 2637/4400) **
Eurofins Ntd Llc (ga)	RCV000035358	SCV000110272	benign	not specified	2014-03-17	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000132147	SCV000187218	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: 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.
PreventionGenetics, part of Exact Sciences	RCV000035358	SCV000303158	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000144614	SCV000430926	benign	Lynch syndrome 1	2018-01-12	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	RCV000132147	SCV000537335	benign	Hereditary cancer-predisposing syndrome	2015-03-30	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001682713	SCV000604255	benign	not provided	2023-11-30	criteria provided, single submitter	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000144614	SCV000744275	benign	Lynch syndrome 1	2015-09-21	criteria provided, single submitter	clinical testing
Invitae	RCV001519744	SCV001728664	benign	Hereditary nonpolyposis colorectal neoplasms	2024-02-01	criteria provided, single submitter	clinical testing
GeneDx	RCV001682713	SCV001897841	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 29715107, 20931542, 11112663, 22283331, 24689082, 20305446)
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000144614	SCV004015932	benign	Lynch syndrome 1	2023-07-07	criteria provided, single submitter	clinical testing
Pathway Genomics	RCV000144614	SCV000189941	benign	Lynch syndrome 1	2014-07-24	no assertion criteria provided	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000035358	SCV000257145	benign	not specified		no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001353712	SCV000592512	benign	Endometrial carcinoma		no assertion criteria provided	clinical testing	The MSH2 c.1661+12G>A variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located within the consensus splice junction and is listed in dbSNP database as a common polymorphism (dbSNP ID: rs3732183).
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000144614	SCV000734201	benign	Lynch syndrome 1		no assertion criteria provided	clinical testing
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000035358	SCV001905807	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000035358	SCV001919049	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000035358	SCV001952762	benign	not specified		no assertion criteria provided	clinical testing