ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.2418C>T (p.Ser806=) (rs770992427)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000162791 SCV000213269 likely benign Hereditary cancer-predisposing syndrome 2014-10-22 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.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000590110 SCV000230041 uncertain significance not provided 2014-10-07 criteria provided, single submitter clinical testing
Invitae RCV001082493 SCV000253094 likely benign Hereditary nonpolyposis colorectal neoplasms 2020-12-01 criteria provided, single submitter clinical testing
GeneDx RCV000590110 SCV000513692 likely benign not provided 2020-05-27 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000178055 SCV000695814 likely benign not specified 2019-09-03 criteria provided, single submitter clinical testing
Color Health, Inc RCV000162791 SCV000911115 likely benign Hereditary cancer-predisposing syndrome 2017-10-27 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000590110 SCV001552846 likely benign not provided no assertion criteria provided clinical testing The MSH6 p.Ser806= variant was not identified in the literature nor was it identified in the COGR, UMD-LSDB, Zhejiang University Database, Mismatch Repair Genes Variant Database, and or Insight Hereditary Tumors database. The variant was identified in dbSNP (ID: rs770992427) as "With other allele"), ClinVar (classified as likely benign by Ambry Genetics, Invitae, and GeneDx and as uncertain significance by two clinical laboratories: EGL Genetic Diagnostics and Integrated Genetics/Laboratory Corporation of America), and in Cosmic (1x in Haematopoietic and lymphoid tissue). The variant was identified in control databases in 5 of 276156 chromosomes at a frequency of 0.00002 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: European in 4 of 125786 chromosomes (freq: 0.00003), and East Asian in 1 of 18860 chromosomes (freq: 0.00005); it was not observed in the African, Other, Latino, Ashkenazi Jewish, Finnish, and or South Asian populations. The p.Ser806= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, the c.2418C nucleotide is weakly conserved and 5 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) 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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