ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.3246G>A (p.Pro1082=) (rs3136351)

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
Ambry Genetics RCV000163801 SCV000214384 likely benign Hereditary cancer-predisposing syndrome 2014-12-28 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000724321 SCV000230868 uncertain significance not provided 2014-10-30 criteria provided, single submitter clinical testing
Invitae RCV001085889 SCV000260070 benign Hereditary nonpolyposis colon cancer 2019-12-31 criteria provided, single submitter clinical testing
Counsyl RCV000410558 SCV000489464 likely benign Hereditary nonpolyposis colorectal cancer type 5 2016-10-07 criteria provided, single submitter clinical testing
Color RCV000163801 SCV000685371 likely benign Hereditary cancer-predisposing syndrome 2015-04-08 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000202109 SCV000917772 benign not specified 2018-08-13 criteria provided, single submitter clinical testing Variant summary: MSH6 c.3246G>A alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The observed variant frequency within Ashkenazi Jewish control individuals in the gnomAD database is approximately 8-fold of the estimated maximal expected allele frequency for a pathogenic variant in MSH6 causing Lynch Syndrome phenotype (0.00014), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Ashkenazi Jewish origin. To our knowledge, no occurrence of c.3246G>A in individuals affected with Lynch Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Co-occurrences with other pathogenic variant(s) have been reported (CHEK2 c.1263delT , p.Ser422fsX15), providing supporting evidence for a benign role. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000202109 SCV000257245 uncertain significance not specified no assertion criteria provided research
True Health Diagnostics RCV000163801 SCV000886689 likely benign Hereditary cancer-predisposing syndrome 2018-07-13 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.