ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.317G>A (p.Arg106Lys) (rs41295286)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000076564 SCV000107594 no known pathogenicity Lynch syndrome 2013-09-05 reviewed by expert panel research Multifactorial likelihood analysis posterior probability <0.001
GeneDx RCV000588805 SCV000149434 likely benign not provided 2019-11-26 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 22949387, 22290698, 18033691, 16736289)
Ambry Genetics RCV000115525 SCV000172850 benign Hereditary cancer-predisposing syndrome 2015-03-10 criteria provided, single submitter clinical testing Co-occurence with a mutation in another gene that clearly explains a proband's phenotype;Does not segregate with disease in family study (genes with incomplete penetrance);In silico models in agreement (benign);Other data supporting benign classification
Pathway Genomics RCV000172812 SCV000223778 benign Lynch syndrome I 2014-10-30 criteria provided, single submitter clinical testing
Invitae RCV001083191 SCV000284165 likely benign Hereditary nonpolyposis colorectal neoplasms 2020-11-14 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000588805 SCV000696260 likely benign not provided 2016-08-01 criteria provided, single submitter clinical testing Variant summary: The MSH2 c.317G>A (p.Arg106Lys) variant involves the alteration of a non-conserved nucleotide. 4/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). This variant was found in 9/123686 control chromosomes at a frequency of 0.0000728, which does not exceed the estimated maximal expected allele frequency of a pathogenic MSH2 variant (0.0005683). This variant has been reported in a proband from LS family with lack of co-segregation of this variant with disease. This patient also carried a pathogenic variant in MLH1, which could explain the patients phenotype. The variant of interest has also been reported in a case-control study with comparable allele frequency detected in the control and case cohorts. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign/likely benign and two clinical labs classified this variant as VUS, all without evidence to independently evaluate. Taken together, the variant was classified as likely benign until additional information becomes available.
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000172812 SCV000744265 benign Lynch syndrome I 2015-09-21 criteria provided, single submitter clinical testing
Color Health, Inc RCV000115525 SCV000910795 benign Hereditary cancer-predisposing syndrome 2016-10-03 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000588805 SCV001134360 uncertain significance not provided 2018-12-13 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000202010 SCV000257184 uncertain significance not specified no assertion criteria provided research
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000202010 SCV001799568 benign not specified no assertion criteria provided clinical testing
Clinical Genetics,Academic Medical Center RCV000588805 SCV001925834 likely benign not provided no assertion criteria provided clinical testing

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