rs1057518834

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The NM_004006.3(DMD):​c.177del​(p.Gln60LysfsTer15) 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 Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 23)

Consequence

DMD
NM_004006.3 frameshift

Scores

Not classified

Clinical Significance

Likely pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: -0.183
Variant links:
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 12 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-32849736-GC-G is Pathogenic according to our data. Variant chrX-32849736-GC-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 374010.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-32849736-GC-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DMDNM_004006.3 linkuse as main transcriptc.177del p.Gln60LysfsTer15 frameshift_variant 3/79 ENST00000357033.9 NP_003997.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DMDENST00000357033.9 linkuse as main transcriptc.177del p.Gln60LysfsTer15 frameshift_variant 3/791 NM_004006.3 ENSP00000354923 P4

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
Cov.:
27
GnomAD4 genome
Cov.:
23

ClinVar

Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Dilated cardiomyopathy 3B Pathogenic:1
Likely pathogenic, criteria provided, single submitterclinical testingCentre for Mendelian Genomics, University Medical Centre LjubljanaJan 01, 2016This variant was classified as: Likely pathogenic. -
Myopathy;C0349588:Short stature;C1850830:Exercise-induced myalgia;C1855578:Exercise-induced muscle cramps;C1855579:Exercise-induced muscle stiffness;C1855580:Exercise-induced muscle fatigue;C4021526:Exercise-induced rhabdomyolysis;C4021726:EMG: myopathic abnormalities;C5574742:Decreased body weight Pathogenic:1
Likely pathogenic, criteria provided, single submitterclinical testingCentre for Mendelian Genomics, University Medical Centre LjubljanaDec 04, 2015- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1057518834; hg19: chrX-32867853; API