Submissions for variant NM_000251.3(MSH2):c.211+9C>G

gnomAD frequency: 0.55454  dbSNP: rs2303426

Total submissions: 21

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT)	RCV000030249	SCV000107420	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	RCV000030249	SCV000052916	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	RCV000035360	SCV000059008	benign	not specified	2012-12-03	criteria provided, single submitter	clinical testing	211+9C>G in intron 1 of MSH2: This variant is not expected to have clinical sign ificance because it is not located within the conserved +/- 1, 2 invariant regio n. It has been identified in 36% (3011/8418) of European American chromosomes fr om a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washi ngton.edu/EVS/; rs23033426). 211+9C>G in intron 1 of MSH2 (rs23033426; allele f requency= 36%, 3011/8418) **
Eurofins Ntd Llc (ga)	RCV000035360	SCV000110275	benign	not specified	2015-05-27	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000035360	SCV000303162	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000144620	SCV000430910	benign	Lynch syndrome 1	2018-01-13	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	RCV000448740	SCV000537324	benign	Hereditary cancer-predisposing syndrome	2014-12-01	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001642243	SCV000604250	benign	not provided	2023-11-30	criteria provided, single submitter	clinical testing
Invitae	RCV000535550	SCV000625350	benign	Hereditary nonpolyposis colorectal neoplasms	2024-02-01	criteria provided, single submitter	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000144620	SCV000744264	benign	Lynch syndrome 1	2015-09-21	criteria provided, single submitter	clinical testing
GeneDx	RCV001642243	SCV001860169	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 30093976)
Sema4, Sema4	RCV000448740	SCV002534446	benign	Hereditary cancer-predisposing syndrome	2020-10-19	criteria provided, single submitter	curation
Ambry Genetics	RCV000448740	SCV002726369	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.
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000144620	SCV004015930	benign	Lynch syndrome 1	2023-07-07	criteria provided, single submitter	clinical testing
Pathway Genomics	RCV000144620	SCV000189947	benign	Lynch syndrome 1	2014-07-24	no assertion criteria provided	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000035360	SCV000257168	benign	not specified		no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001353423	SCV000592456	benign	Carcinoma of colon		no assertion criteria provided	clinical testing	The c.211+9C>G variant is not expected to have clinical significance because it is not located in the conserved region of the splicing consensus sequence. Furthermore, this variant is reported as a common polymorphism in dbSNP (rs2303426) and reported as a benign polymorphism in the literature. Average Heterozygosity: 0.488+/-0.075
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000144620	SCV000734196	benign	Lynch syndrome 1		no assertion criteria provided	clinical testing
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000035360	SCV001906300	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000035360	SCV001925124	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000035360	SCV001953620	benign	not specified		no assertion criteria provided	clinical testing