chrX-32699286-A-T
Variant summary
Our verdict is Benign. The variant received -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. 11/19 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. D219H) has been classified as Uncertain significance.
Frequency
Consequence
NM_004006.3 missense
Scores
Clinical Significance
Conservation
Publications
- Becker muscular dystrophyInheritance: XL Classification: DEFINITIVE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet
- dilated cardiomyopathy 3BInheritance: XL Classification: DEFINITIVE Submitted by: Ambry Genetics
- Duchenne and Becker muscular dystrophyInheritance: XL Classification: DEFINITIVE Submitted by: Myriad Women’s Health
- Duchenne muscular dystrophyInheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Orphanet
- progressive muscular dystrophyInheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
- familial isolated dilated cardiomyopathyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- non-syndromic X-linked intellectual disabilityInheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
- symptomatic form of muscular dystrophy of Duchenne and Becker in female carriersInheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Our verdict: Benign. The variant received -11 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DMD | ENST00000357033.9 | c.657T>A | p.Asp219Glu | missense_variant | Exon 8 of 79 | 1 | NM_004006.3 | ENSP00000354923.3 |
Frequencies
GnomAD3 genomes AF: 0.00000896 AC: 1AN: 111636Hom.: 0 Cov.: 22 show subpopulations
GnomAD2 exomes AF: 0.0000219 AC: 4AN: 182437 AF XY: 0.0000149 show subpopulations
GnomAD4 exome AF: 0.0000532 AC: 58AN: 1089771Hom.: 0 Cov.: 29 AF XY: 0.0000590 AC XY: 21AN XY: 355673 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.00000896 AC: 1AN: 111636Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 33840 show subpopulations
ClinVar
Submissions by phenotype
Duchenne muscular dystrophy;C0878544:Cardiomyopathy;C0917713:Becker muscular dystrophy;na:Dystrophin deficiency Uncertain:1
- -
Cardiovascular phenotype Uncertain:1
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 hemizygote 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
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at