ClinVar Miner

Submissions for variant NM_004006.3(DMD):c.5163G>C (p.Lys1721Asn)

gnomAD frequency: 0.00021  dbSNP: rs72468630
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000537267 SCV000625916 benign Duchenne muscular dystrophy 2024-01-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000621389 SCV000735130 benign Cardiovascular phenotype 2015-09-04 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.
Illumina Laboratory Services, Illumina RCV001167366 SCV001329856 likely benign Dilated cardiomyopathy 3B 2017-06-15 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001290603 SCV001478695 likely benign not specified 2021-01-04 criteria provided, single submitter clinical testing Variant summary: DMD c.5163G>C (p.Lys1721Asn) 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. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0011 in 177459 control chromosomes, predominantly at a frequency of 0.013 within the East Asian subpopulation in the gnomAD database, including 1 homozygote. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 1179 fold of the estimated maximal expected allele frequency for a pathogenic variant in DMD causing Dystrophinopathies phenotype (1.1e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. c.5163G>C has been reported in the literature in at least an individual affected with Dystrophinopathies (e.g. Kong_2019). This report however, does not provide unequivocal conclusions about association of the variant with Dystrophinopathies. Co-occurrence with another likely pathogenic variant has been reported (DMD c.5476G>T, p.E1826X) in our internal database, providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submitters (evaluation after 2014) cite the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
GeneDx RCV001637065 SCV001851703 benign not provided 2018-09-20 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 19937601, 29604111)
Genetic Services Laboratory, University of Chicago RCV001290603 SCV002068930 benign not specified 2018-04-20 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001637065 SCV004564922 benign not provided 2023-11-09 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004537896 SCV004730338 benign DMD-related disorder 2019-04-18 criteria provided, single submitter clinical testing This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Natera, Inc. RCV001829548 SCV002093532 benign Becker muscular dystrophy; Duchenne muscular dystrophy; Cardiomyopathy; Dystrophin deficiency 2020-04-12 no assertion criteria provided clinical testing

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