ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.792+5A>G (rs267607935)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129148 SCV000183869 likely benign Hereditary cancer-predisposing syndrome 2018-07-26 criteria provided, single submitter clinical testing In silico models in agreement (benign);Other data supporting benign classification
Counsyl RCV000410638 SCV000489026 uncertain significance Lynch syndrome I 2016-08-05 criteria provided, single submitter clinical testing
GeneDx RCV000440249 SCV000513654 likely benign not specified 2017-08-07 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 RCV000524421 SCV000548228 likely benign Hereditary nonpolyposis colorectal neoplasms 2020-12-01 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000589455 SCV000696283 uncertain significance not provided 2016-12-16 criteria provided, single submitter clinical testing Variant summary: The MSH2 c.792+5A>G variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a benign outcome for this variant. 5/5 splice prediction tools predict the variant to result in the strengthening of a cannonical splice donor site. However, these predictions have yet to be confirmed by functional studies. This variant was found in 3/119958 control chromosomes at a frequency of 0.000025, which does not exceed the estimated maximal expected allele frequency of a pathogenic MSH2 variant (0.0005683). The variant was reported in an affected individual in the literature, without strong evidence for causality. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance. Taken together, this variant is classified as VUS.
Color Health, Inc RCV000129148 SCV000902909 likely benign Hereditary cancer-predisposing syndrome 2016-02-22 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001355416 SCV001550297 uncertain significance Malignant tumor of breast no assertion criteria provided clinical testing The MSH2 c.792+5A>G variant was not identified in the literature nor was it identified in the following databases: COGR, Cosmic, MutDB, UMD-LSDB, Zhejiang Colon Cancer Database, or the Mismatch Repair Genes Variant Database. The variant was identified in dbSNP (ID: rs267607935) as “With Uncertain significance allele”, ClinVar (classified as uncertain significance by InSIGHT, Counsyl, Invitae and Laboratory Corporation of America; and likely benign by Ambry Genetics and GeneDx), Clinvitae (5x), Insight Hereditary Tumors Database (1x), and in control databases in 7 of 245164 chromosomes at a frequency of 0.00003 (Genome Aggregation Database Feb 27, 2017). It was observed in the European Non-Finnish population in 7 of 111216 chromosomes (freq: 0.00006) but not in the African, Other, Latino, Ashkenazi Jewish, East Asian, European Finnish, and South Asian populations. The c.792+5A>G variant is located in the 5' splice region but does not affect the invariant +1 and +2 positions. However, positions +3 to +6 are part of the splicing consensus sequence and variants involving these positions sometimes affect splicing. In addition, 3 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing. However, this information is not predictive enough to assume pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.

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.