ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.1077-10T>C (rs17224360)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 19
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000030235 SCV000107039 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 RCV000030235 SCV000052902 benign Lynch syndrome 2011-08-18 criteria provided, single submitter curation Converted during submission to Benign.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000179738 SCV000232034 benign not specified 2014-12-03 criteria provided, single submitter clinical testing
Invitae RCV000524329 SCV000262456 benign Hereditary nonpolyposis colorectal neoplasms 2020-11-26 criteria provided, single submitter clinical testing
Vantari Genetics RCV000210766 SCV000267050 benign Hereditary cancer-predisposing syndrome 2015-12-02 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000179738 SCV000303155 benign not specified criteria provided, single submitter clinical testing
Color Health, Inc RCV000210766 SCV000537358 benign Hereditary cancer-predisposing syndrome 2014-12-09 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000179738 SCV000604251 benign not specified 2018-07-22 criteria provided, single submitter clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000602995 SCV000744273 benign Lynch syndrome I 2015-09-21 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000602995 SCV000745637 benign Lynch syndrome I 2015-10-07 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000602995 SCV001302370 likely benign Lynch syndrome I 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
GeneDx RCV001668139 SCV001891368 benign not provided 2015-03-03 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000179738 SCV000257121 benign not specified no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000030235 SCV000592488 benign Lynch syndrome no assertion criteria provided clinical testing The MSH2 c.1077-10T>C variant was identified in at least 4 of 254 proband chromosomes (frequency: 0.016) from individuals with colon cancer and in at least 5 of 226 control chromosomes (frequency: 0.022) (Borresen 1995, Chen-Shtoyerman, Swensen 1997, Tournier 2008). The variant was also identified in the “Mismatch Repair Genes Variant Database”, “MMR Gene Unclassified Variants Database”, “InSiGHT Colon Cancer Database”, and in UMD (39X as a neutral variant). The c.1077-10T>C variant is located in the 3' splice region but does not affect the invariant -1 and -2 positions; however, positions -3 and -5 to -12 are part of the splicing consensus sequence and variants involving these positions sometimes affect splicing. Four in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, HumanSpliceFinder) do not predict a greater than 10% difference in splicing, and an ex vivo splicing assay found no effect of the variant on splicing (Tournier 2008 18561205). The variant was listed in dbSNP (ID: rs17224360) “With non-pathogenic allele”, with a global minor allele frequency of 0.007 (1000 Genomes Project), and a frequency of 0.017 in 60 HapMap individuals, increasing the likelihood that this is a low frequency benign variant in certain populations of origin. In addition, several studies list or describe this variant as a polymorphism or non-pathogenic variant (Borresen 1995, Chen-Shtoyerman, Desai 2000, Jung 2006, Rubio-Del-Campo 2007, Swensen 1997, Tournier 2008). Furthermore, this variant was identified in one individual from our lab with a pathogenic variant co-occurring, increasing the likelihood of this variant having no clinical significance. In summary, based on the above information, this variant meets our laboratory's criteria to be classified as benign.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000602995 SCV000734199 benign Lynch syndrome I no assertion criteria provided clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000179738 SCV001800051 benign not specified no assertion criteria provided clinical testing
Clinical Genetics Laboratory, Department of Pathology,Netherlands Cancer Institute RCV000179738 SCV001905862 benign not specified no assertion criteria provided clinical testing
Clinical Genetics,Academic Medical Center RCV000179738 SCV001926141 benign not specified no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000179738 SCV001959846 benign not specified no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.