ClinVar Miner

Submissions for variant NM_004006.3(DMD):c.8858C>A (p.Ala2953Asp)

gnomAD frequency: 0.00001  dbSNP: rs773941387
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000692788 SCV000820631 uncertain significance Duchenne muscular dystrophy 2022-08-24 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 2953 of the DMD protein (p.Ala2953Asp). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with DMD-related conditions. ClinVar contains an entry for this variant (Variation ID: 571602). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV002369866 SCV002684354 uncertain significance Cardiovascular phenotype 2022-08-31 criteria provided, single submitter clinical testing The p.A2953D variant (also known as c.8858C>A), located in coding exon 59 of the DMD gene, results from a C to A substitution at nucleotide position 8858. The alanine at codon 2953 is replaced by aspartic acid, an amino acid with dissimilar properties. Based on data from gnomAD, the A allele has an overall frequency of 0.0006% (1/181600) total alleles studied, with 0 hemizygote(s) observed. The highest observed frequency was 0.0037% (1/27262) of Latino alleles. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001825348 SCV002080229 uncertain significance Becker muscular dystrophy; Duchenne muscular dystrophy; Cardiomyopathy; Dystrophin deficiency 2018-09-16 no assertion criteria provided clinical testing

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