ClinVar Miner

Submissions for variant NM_004006.3(DMD):c.821A>G (p.Tyr274Cys)

gnomAD frequency: 0.00013  dbSNP: rs745868830
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000596666 SCV000703638 uncertain significance not provided 2016-11-30 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000990742 SCV000751565 benign Duchenne muscular dystrophy 2024-01-31 criteria provided, single submitter clinical testing
GeneDx RCV000596666 SCV000976800 likely benign not provided 2021-05-04 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 19937601)
Mendelics RCV000990742 SCV001141773 likely benign Duchenne muscular dystrophy 2019-05-28 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001193796 SCV001362911 benign not specified 2019-02-25 criteria provided, single submitter clinical testing Variant summary: DMD c.821A>G (p.Tyr274Cys) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00013 in 199695 control chromosomes including 11 hemizygotes. This frequency is not significantly higher than expected for a pathogenic variant in DMD causing Dystrophinopathies (0.00013 vs 0.011). c.821A>G has been reported in the literature in individuals affected with Dystrophinopathies (Flanigan_2009, Luce_2019). One of the individuals was a male who carried another pathogenic DMD variant, c.3427dupC (p.Gln1143fsX34)(Luce_2018), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submissions from clinical diagnostic laboratories (evalution after 2014) cite the variant as uncertain significance and benign. Based on the evidence outlined above, the variant was classified as benign.
Ambry Genetics RCV002431748 SCV002681255 benign Cardiovascular phenotype 2020-07-22 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, 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.
Natera, Inc. RCV001834876 SCV002090469 likely benign Becker muscular dystrophy; Duchenne muscular dystrophy; Cardiomyopathy; Dystrophin deficiency 2018-06-11 no assertion criteria provided clinical testing

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