ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.211+8C>T (rs267607916)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000427874 SCV000513648 benign not specified 2015-08-15 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV001085835 SCV000559218 likely benign Hereditary nonpolyposis colorectal neoplasms 2020-11-30 criteria provided, single submitter clinical testing
Color Health, Inc RCV000579968 SCV000685010 likely benign Hereditary cancer-predisposing syndrome 2015-11-12 criteria provided, single submitter clinical testing
Counsyl RCV000663062 SCV000786123 likely benign Lynch syndrome I 2018-02-27 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759110 SCV000888216 likely benign not provided 2018-08-14 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000427874 SCV000917711 uncertain significance not specified 2018-01-12 criteria provided, single submitter clinical testing Variant summary: The MSH2 c.211+8C>T variant involves the alteration of a non-conserved intronic nucleotide and 4/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts the elimination of ESE binding sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 10/242066 control chromosomes (gnomAD), predominantly observed in the European (Non-Finnish) subpopulation at a frequency of 0.000092 (10/108416). This frequency does not exceed the estimated maximal expected allele frequency of a pathogenic MSH2 variant (0.0005683). Multiple clinical diagnostic laboratories classified this variant as "likely benign/benign." The variant of interest has not, to our knowledge, been reported in affected individuals via publications. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a "Variant of Uncertain Significance - Possibly Benign," until additional information becomes available.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000759110 SCV001152270 uncertain significance not provided 2017-02-01 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000759110 SCV001549862 likely benign not provided no assertion criteria provided clinical testing The MSH2 c.211+8C>T variant was not identified in the literature nor was it identified in the UMD-LSDB database. The variant was identified in dbSNP (rs267607916) as “with likely benign, uncertain significance allele” and ClinVar (classified as likely benign by Invitae, Counsyl, Color and Quest Diagnostics, benign by GeneDx and uncertain significance by Integrated Genetics). The variant was identified in control databases in 10 of 246,872 chromosomes at a frequency of 0.00004 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: European in 10 of 111,074 chromosomes (freq: 0.00009), but not in the African, Latino, Ashkenazi Jewish, East Asian, Finnish, Other and South Asian populations. The variant occurs at a weakly conserved nucleotide outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

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.