ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.-2G>T (rs374748889)

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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 RCV000131214 SCV000186165 likely benign Hereditary cancer-predisposing syndrome 2018-07-17 criteria provided, single submitter clinical testing Other data supporting benign classification
GeneDx RCV000212624 SCV000211375 likely benign not specified 2017-09-07 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 RCV000199508 SCV000254236 uncertain significance Lynch syndrome 2015-06-13 criteria provided, single submitter clinical testing This sequence change falls in the 5' UTR promoter region of the MSH6 gene. It does not change the encoded amino acid sequence of the MSH6 protein. This variant has not been published in the literature and is present in population databases (rs374748889, 0.02%). ClinVar contains an entry for this variant (RCV000131214). In summary, this is a rare 5' non-coding change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000212624 SCV000592560 uncertain significance not specified 2012-12-17 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000588323 SCV000601552 uncertain significance not provided 2019-03-12 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000588323 SCV000695836 uncertain significance not provided 2016-11-10 criteria provided, single submitter clinical testing Variant summary: The MSH6 c.-2G>T variant located in the Kozak sequence of MSH6 involves the alteration of a non-conserved nucleotide. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict the loss of a canonical splice donor site. However, these predictions have yet to be confirmed by functional studies. This variant was found in 2/115448 control chromosomes at a frequency of 0.0000173, which does not exceed the estimated maximal expected allele frequency of a pathogenic MSH6 variant (0.0001421). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available.
Color RCV000131214 SCV000910735 likely benign Hereditary cancer-predisposing syndrome 2015-04-25 criteria provided, single submitter clinical testing

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