rs398124012
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_004006.3(DMD):c.6391_6392del(p.Gln2131AsnfsTer3) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. Q2131Q) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 23)
Consequence
DMD
NM_004006.3 frameshift
NM_004006.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.57
Genes affected
DMD (HGNC:2928): (dystrophin) This gene spans a genomic range of greater than 2 Mb and encodes a large protein containing an N-terminal actin-binding domain and multiple spectrin repeats. The encoded protein forms a component of the dystrophin-glycoprotein complex (DGC), which bridges the inner cytoskeleton and the extracellular matrix. Deletions, duplications, and point mutations at this gene locus may cause Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), or cardiomyopathy. Alternative promoter usage and alternative splicing result in numerous distinct transcript variants and protein isoforms for this gene. [provided by RefSeq, Dec 2016]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 18 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant X-32216961-TTG-T is Pathogenic according to our data. Variant chrX-32216961-TTG-T is described in ClinVar as [Pathogenic]. Clinvar id is 94705.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-32216961-TTG-T is described in Lovd as [Pathogenic]. Variant chrX-32216961-TTG-T is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DMD | NM_004006.3 | c.6391_6392del | p.Gln2131AsnfsTer3 | frameshift_variant | 44/79 | ENST00000357033.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DMD | ENST00000357033.9 | c.6391_6392del | p.Gln2131AsnfsTer3 | frameshift_variant | 44/79 | 1 | NM_004006.3 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 genomes
?
Cov.:
23
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 23
GnomAD4 genome
?
Cov.:
23
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 19, 2015 | - - |
Duchenne muscular dystrophy Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 16, 2016 | This sequence change deletes 2 nucleotides from exon 44 of the DMD mRNA (c.6391_6392delCA), causing a frameshift at codon 2131. This creates a premature translational stop signal (p.Gln2131Asnfs*3) and is expected to result in an absent or disrupted protein product. Loss-of-function variants in DMD are known to be pathogenic. This particular variant has been reported in the literature in individuals affected with Duchenne muscular dystrophies  (PMID: 22678781, 25612904, 16770791). ClinVar contains an entry for this variant (Variation ID: 94705). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
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Calibrated prediction
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Prediction
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at