rs727502994
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_004415.4(DSP):c.5378_5379dup(p.Ala1794ArgfsTer25) 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 (★).
Frequency
Genomes: not found (cov: 32)
Consequence
DSP
NM_004415.4 frameshift
NM_004415.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.22
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 12 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. There are 109 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 6-7581565-T-TAG is Pathogenic according to our data. Variant chr6-7581565-T-TAG is described in ClinVar as [Likely_pathogenic]. Clinvar id is 163231.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DSP | NM_004415.4 | c.5378_5379dup | p.Ala1794ArgfsTer25 | frameshift_variant | 23/24 | ENST00000379802.8 | |
DSP | NM_001008844.3 | c.3583-1074_3583-1073dup | intron_variant | ||||
DSP | NM_001319034.2 | c.4051-1074_4051-1073dup | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DSP | ENST00000379802.8 | c.5378_5379dup | p.Ala1794ArgfsTer25 | frameshift_variant | 23/24 | 1 | NM_004415.4 | P2 | |
DSP | ENST00000418664.2 | c.3583-1074_3583-1073dup | intron_variant | 1 | A2 | ||||
DSP | ENST00000710359.1 | c.4051-1074_4051-1073dup | intron_variant | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Primary dilated cardiomyopathy Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Oct 15, 2013 | The Ala1794fs variant in DSP has not been previously reported in individuals wit h cardiomyopathy and data from large population studies is insufficient to asses s its frequency. This frameshift variant is predicted to alter the protein?s ami no acid sequence beginning at position 1794 and lead to a premature termination codon 25 amino acids downstream. This alteration is then predicted to lead to a truncated protein. In summary, this variant is likely pathogenic, though additio nal studies are required to fully establish its clinical significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at