ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.4002-8A>C

gnomAD frequency: 0.00001  dbSNP: rs778957100
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000205656 SCV000260078 likely benign Hereditary nonpolyposis colorectal neoplasms 2023-12-20 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000579624 SCV000685479 likely benign Hereditary cancer-predisposing syndrome 2016-06-20 criteria provided, single submitter clinical testing
GeneDx RCV001711614 SCV001941872 benign not provided 2015-07-21 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 30093976)
Sema4, Sema4 RCV000579624 SCV002536311 uncertain significance Hereditary cancer-predisposing syndrome 2021-08-06 criteria provided, single submitter curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV002267938 SCV002552384 likely benign not specified 2023-08-15 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001711614 SCV004222036 likely benign not provided 2023-05-09 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV003997591 SCV004815789 likely benign Lynch syndrome 2024-02-05 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001354582 SCV001549230 likely benign Carcinoma of colon no assertion criteria provided clinical testing The MSH6 c.4002-8A>C variant was not identified in the literature nor was it identified in the UMD-LSDB database. The variant was identified in dbSNP (ID: rs778957100) as "With Likely benign allele", ClinVar (classified as likely benign by Invitae and Color). The variant was identified in our laboratory with a co-occurring pathogenic MSH2 variant (c.2444delA, p.Tyr815PhefsX3), increasing the likelihood that the c.4002-8A>C variant does not have clinical significance. The variant was not identified in the following control databases: the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). The c.4002-8A>C 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. However, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

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