chrX-32454660-A-C
Variant names:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PVS1_ModeratePP5
The NM_004006.3(DMD):c.3603+2T>G variant causes a splice donor, intron change involving the alteration of a conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 14)
Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )
Failed GnomAD Quality Control
Consequence
DMD
NM_004006.3 splice_donor, intron
NM_004006.3 splice_donor, intron
Scores
3
1
1
Splicing: ADA: 1.000
2
Clinical Significance
Conservation
PhyloP100: 9.30
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 Uncertain_significance. Variant got 3 ACMG points.
PVS1
Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.0154639175 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.
PP5
Variant X-32454660-A-C is Pathogenic according to our data. Variant chrX-32454660-A-C is described in ClinVar as [Pathogenic]. Clinvar id is 11229.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-32454660-A-C is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DMD | ENST00000357033.9 | c.3603+2T>G | splice_donor_variant, intron_variant | Intron 26 of 78 | 1 | NM_004006.3 | ENSP00000354923.3 |
Frequencies
GnomAD3 genomes Cov.: 14
GnomAD3 genomes
Cov.:
14
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 820138Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0AN XY: 237648
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
820138
Hom.:
Cov.:
24
AF XY:
AC XY:
0
AN XY:
237648
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 14
GnomAD4 genome
Cov.:
14
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Duchenne muscular dystrophy Pathogenic:1
Jan 01, 1994
OMIM
Significance: Pathogenic
Review Status: no assertion criteria provided
Collection Method: literature only
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Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
FATHMM_MKL
Pathogenic
D
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: 2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at