Submissions for variant NM_000251.3(MSH2):c.1511-9A>T

gnomAD frequency: 0.09123  dbSNP: rs12998837

Total submissions: 22

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT)	RCV000030240	SCV000107203	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	RCV000030240	SCV000052907	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	RCV000035357	SCV000059005	benign	not specified	2012-12-03	criteria provided, single submitter	clinical testing	1511-9A>T in intron 9 of MSH2: This variant is not expected to have clinical sig nificance because it is not located within the conserved +/- 1, 2 invariant regi on. It has been identified in 12.2% (1053/8600) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.wa shington.edu/EVS/; rs12998837). 1511-9A>T in intron 9 of MSH2 (rs12998837; alle le frequency= 12.2%, 1053/8600) **
Eurofins Ntd Llc (ga)	RCV000035357	SCV000110271	benign	not specified	2013-10-24	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000132430	SCV000187524	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.
Color Diagnostics, LLC DBA Color Health	RCV000132430	SCV000292090	benign	Hereditary cancer-predisposing syndrome	2022-01-02	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000035357	SCV000303157	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000144613	SCV000430924	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001527747	SCV000604254	benign	not provided	2023-11-28	criteria provided, single submitter	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000144613	SCV000744274	benign	Lynch syndrome 1	2015-09-21	criteria provided, single submitter	clinical testing
Invitae	RCV000860043	SCV000999955	benign	Hereditary nonpolyposis colorectal neoplasms	2024-02-01	criteria provided, single submitter	clinical testing
Mendelics	RCV000144613	SCV001135734	benign	Lynch syndrome 1	2019-05-28	criteria provided, single submitter	clinical testing
GeneDx	RCV001527747	SCV001738876	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002490417	SCV002801217	likely benign	Lynch syndrome 1; Muir-Torré syndrome; Mismatch repair cancer syndrome 2	2022-05-16	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000144613	SCV004015946	benign	Lynch syndrome 1	2023-07-07	criteria provided, single submitter	clinical testing
Pathway Genomics	RCV000144613	SCV000189940	benign	Lynch syndrome 1	2014-07-24	no assertion criteria provided	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000035357	SCV000257143	benign	not specified		no assertion criteria provided	research
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001354031	SCV000592504	benign	Carcinoma of colon		no assertion criteria provided	clinical testing	This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located near a splice junction, is listed in dbSNP (rs12998837) with a frequency of ~10%, and is reported as benign in over 10 publications.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000144613	SCV000734200	benign	Lynch syndrome 1		no assertion criteria provided	clinical testing
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000035357	SCV001906266	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000035357	SCV001919169	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000035357	SCV001958469	benign	not specified		no assertion criteria provided	clinical testing