ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.2187C>A (p.Ala729=) (rs375610656)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000202207 SCV000211355 benign not specified 2014-10-02 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 RCV000588900 SCV000253093 likely benign not provided 2019-01-30 criteria provided, single submitter clinical testing
Ambry Genetics RCV000563596 SCV000669978 likely benign Hereditary cancer-predisposing syndrome 2016-04-27 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Synonymous alterations with insufficient evidence to classify as benign
Color RCV000563596 SCV000685263 likely benign Hereditary cancer-predisposing syndrome 2015-09-30 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000588900 SCV000695802 likely benign not provided 2017-03-30 criteria provided, single submitter clinical testing Variant summary: The MSH6 c.2187C>A (p.Ala729Ala) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 4/121168 control chromosomes, predominantly observed in the African subpopulation at a frequency of 0.000386 (4/10352). This frequency is about 3 times the estimated maximal expected allele frequency of a pathogenic MSH6 variant (0.0001421), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. 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. Taken together, due to the lack of effect on amino acid sequence, the lack of predicted effect on splicing, and the frequency of the variant in the African subpopulation, this variant is classified as likley benign.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000202207 SCV000257220 likely benign not specified no assertion criteria provided research

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