rs771312947
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6BS1BS2
The NM_004006.3(DMD):c.657T>A(p.Asp219Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000491 in 1,201,407 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 21 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D219V) has been classified as Uncertain significance.
Frequency
Consequence
NM_004006.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DMD | NM_004006.3 | c.657T>A | p.Asp219Glu | missense_variant | 8/79 | ENST00000357033.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DMD | ENST00000357033.9 | c.657T>A | p.Asp219Glu | missense_variant | 8/79 | 1 | NM_004006.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00000896 AC: 1AN: 111636Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 33840
GnomAD3 exomes AF: 0.0000219 AC: 4AN: 182437Hom.: 0 AF XY: 0.0000149 AC XY: 1AN XY: 67321
GnomAD4 exome AF: 0.0000532 AC: 58AN: 1089771Hom.: 0 Cov.: 29 AF XY: 0.0000590 AC XY: 21AN XY: 355673
GnomAD4 genome ? AF: 0.00000896 AC: 1AN: 111636Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 33840
ClinVar
Submissions by phenotype
Duchenne muscular dystrophy;C0878544:Cardiomyopathy;C0917713:Becker muscular dystrophy;na:Dystrophin deficiency Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Mar 18, 2020 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 23, 2022 | The p.D219E variant (also known as c.657T>A), located in coding exon 8 of the DMD gene, results from a T to A substitution at nucleotide position 657. The aspartic acid at codon 219 is replaced by glutamic acid, an amino acid with highly similar properties. Based on data from gnomAD, the A allele has an overall frequency of 0.0022% (4/182437) total alleles studied, with 1 hemizygotes observed. The highest observed frequency was 0.0289% (4/13828) of East Asian alleles. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Duchenne muscular dystrophy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at