rs397514045
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_004415.4(DSP):c.7780del(p.Ser2594ProfsTer9) 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 (no stars). Synonymous variant affecting the same amino acid position (i.e. I2593I) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 32)
Consequence
DSP
NM_004415.4 frameshift
NM_004415.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.45
Genes affected
DSP (HGNC:3052): (desmoplakin) This gene encodes a protein that anchors intermediate filaments to desmosomal plaques and forms an obligate component of functional desmosomes. Mutations in this gene are the cause of several cardiomyopathies and keratodermas, including skin fragility-woolly hair syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 24 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 6-7585039-AT-A is Pathogenic according to our data. Variant chr6-7585039-AT-A is described in ClinVar as [Pathogenic]. Clinvar id is 60561.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-7585039-AT-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DSP | NM_004415.4 | c.7780del | p.Ser2594ProfsTer9 | frameshift_variant | 24/24 | ENST00000379802.8 | |
DSP | NM_001319034.2 | c.6451del | p.Ser2151ProfsTer9 | frameshift_variant | 24/24 | ||
DSP | NM_001008844.3 | c.5983del | p.Ser1995ProfsTer9 | frameshift_variant | 24/24 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DSP | ENST00000379802.8 | c.7780del | p.Ser2594ProfsTer9 | frameshift_variant | 24/24 | 1 | NM_004415.4 | P2 | |
DSP | ENST00000418664.2 | c.5983del | p.Ser1995ProfsTer9 | frameshift_variant | 24/24 | 1 | A2 | ||
DSP | ENST00000710359.1 | c.6451del | p.Ser2151ProfsTer9 | frameshift_variant | 24/24 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 36
GnomAD4 exome
Cov.:
36
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Arrhythmogenic cardiomyopathy with wooly hair and keratoderma Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 01, 2013 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at