ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.766G>A (p.Ala256Thr)

gnomAD frequency: 0.00014  dbSNP: rs377403073
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 10
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000160627 SCV000211226 uncertain significance not provided 2023-06-16 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Observed in individuals with ovarian and renal cancer (Pal et al., 2012; Yehia et al., 2018); This variant is associated with the following publications: (PMID: 23047549, 29684080, 21120944, 18822302)
Invitae RCV000196535 SCV000254429 likely benign Hereditary nonpolyposis colorectal neoplasms 2024-01-30 criteria provided, single submitter clinical testing
Ambry Genetics RCV000491536 SCV000580572 likely benign Hereditary cancer-predisposing syndrome 2021-07-20 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: 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.
Counsyl RCV000662661 SCV000785350 uncertain significance Lynch syndrome 1 2017-07-20 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000160627 SCV000888231 uncertain significance not provided 2019-01-30 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000491536 SCV000911380 likely benign Hereditary cancer-predisposing syndrome 2016-01-07 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000491536 SCV002526744 uncertain significance Hereditary cancer-predisposing syndrome 2021-12-29 criteria provided, single submitter curation
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002265637 SCV002547927 uncertain significance not specified 2022-05-10 criteria provided, single submitter clinical testing Variant summary: MSH2 c.766G>A (p.Ala256Thr) results in a non-conservative amino acid change located in the DNA mismatch repair protein MutS, connector domain of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4.8e-05 in 251288 control chromosomes, predominantly at a frequency of 0.00074 within the African or African-American subpopulation in the gnomAD database. c.766G>A has been reported in the literature in an individual affected with ovarian cancer (Pal_2012). This report does not provide unequivocal conclusions about association of the variant with Prostate Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Five submitters classified the variant as VUS while one classified it as likely benign. Based on the evidence outlined above, the variant was classified as VUS.
Myriad Genetics, Inc. RCV000662661 SCV004018310 benign Lynch syndrome 1 2023-03-20 criteria provided, single submitter clinical testing This variant is considered benign. This variant is strongly associated with less severe personal and family histories of cancer, typical for individuals without pathogenic variants in this gene [PMID: 25085752]. Homozygosity for this variant has been confirmed in one or more individuals lacking clinical features consistent with gene-specific recessive disease, indicating that this variant is unlikely to be pathogenic.
Baylor Genetics RCV000662661 SCV004196238 uncertain significance Lynch syndrome 1 2023-09-22 criteria provided, single submitter 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.