X-32454660-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePP5_Moderate
The NM_004006.3(DMD):c.3603+2T>C variant causes a splice donor, intron change involving the alteration of a conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Consequence
NM_004006.3 splice_donor, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DMD | ENST00000357033.9 | c.3603+2T>C | splice_donor_variant, intron_variant | Intron 26 of 78 | 1 | NM_004006.3 | ENSP00000354923.3 |
Frequencies
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: 237646
GnomAD4 genome Cov.: 14
ClinVar
Submissions by phenotype
Duchenne muscular dystrophy Pathogenic:1
This sequence change affects a donor splice site in intron 26 of the DMD gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in DMD are known to be pathogenic (PMID: 16770791, 25007885). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with Duchenne muscular dystrophy (PMID: 19937601, 23536893). ClinVar contains an entry for this variant (Variation ID: 964684). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at