ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.1387-8G>T (rs187525243)

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Total submissions: 20
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000625492 SCV000107164 benign Lynch syndrome I 2018-06-13 reviewed by expert panel curation Multifactorial likelihood analysis posterior probability < 0.001 (0.00017)
GeneDx RCV000202101 SCV000170337 benign not specified 2013-12-12 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 RCV001083687 SCV000252652 benign Hereditary nonpolyposis colorectal neoplasms 2020-11-27 criteria provided, single submitter clinical testing
Vantari Genetics RCV000126811 SCV000267051 benign Hereditary cancer-predisposing syndrome 2015-12-28 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000202101 SCV000303156 likely benign not specified criteria provided, single submitter clinical testing
Color Health, Inc RCV000126811 SCV000537404 benign Hereditary cancer-predisposing syndrome 2015-02-19 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000202101 SCV000595828 likely benign not specified 2017-03-22 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000625492 SCV000745639 likely benign Lynch syndrome I 2015-08-07 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000679289 SCV000805997 likely benign not provided 2016-10-03 criteria provided, single submitter clinical testing
Mendelics RCV000625492 SCV001135729 likely benign Lynch syndrome I 2019-05-28 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000679289 SCV001152277 likely benign not provided 2020-03-01 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000202101 SCV001156595 benign not specified 2018-10-03 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000625492 SCV001304348 likely benign Lynch syndrome I 2019-05-07 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000030239 SCV000052906 benign Lynch syndrome 2015-02-16 no assertion criteria provided clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000202101 SCV000257139 benign not specified no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000030239 SCV000592501 benign Lynch syndrome no assertion criteria provided clinical testing The c.1387-8G>T variant has been reported in the literature in at least 4 of 224 probands who either had CRC or met criteria for Lynch syndrome (Tournier_2008_18561205, Lamberti_2006_17095871, Levene_2003_14574163, Van_Pruijenbroek_2008 18415027). However, population controls were not included in these studies such that the full spectrum of benign variation may not yet have been defined for this gene, increasing the possibility that this may be a benign variant. This variant was identified in the EVS server, dbSNP and the 1000 genomes project as a low frequency variant in both Caucasian and black populations increasing the likelihood this variant is benign. In addition, this variant did not have any effect in an ex-vivo splicing assay (Tournier_2008_18561205) increasing the likelihood that this variant does not have clinical significance. Furthermore, this variant was reported in two studies in two individuals, both had high microsatellite instability (MSI), however, immunohistochemistry for MLH1, MSH2, MSH6 was intact, increasing the likelihood this variant does not result in loss of function of the protein product (Lamberti_2006_17095871, Van_Pruijenbroek_2008 18415027). The c.1387-8G>T variant is located in the 3' splice region but does not affect the invariant -1 and -2 positions. However, positions -3 and -5 to -12 are part of the splicing consensus sequence and variants involving these positions sometimes affect splicing. In summary, based on the above information, this variant is classified as benign.
True Health Diagnostics RCV000126811 SCV000805265 likely benign Hereditary cancer-predisposing syndrome 2018-04-30 no assertion criteria provided clinical testing
Clinical Genetics,Academic Medical Center RCV000679289 SCV001919914 likely benign not provided no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000202101 SCV001928887 benign not specified no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000679289 SCV001956919 likely benign not provided no assertion criteria provided clinical testing

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