rs1060503171
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_Strong
The NM_001927.4(DES):c.1354_1358del(p.Glu452ThrfsTer8) variant causes a frameshift change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. I451I) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 32)
Consequence
DES
NM_001927.4 frameshift
NM_001927.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.86
Genes affected
DES (HGNC:2770): (desmin) This gene encodes a muscle-specific class III intermediate filament. Homopolymers of this protein form a stable intracytoplasmic filamentous network connecting myofibrils to each other and to the plasma membrane. Mutations in this gene are associated with desmin-related myopathy, a familial cardiac and skeletal myopathy (CSM), and with distal myopathies. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 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 17 pathogenic variants in the truncated region.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DES | NM_001927.4 | c.1354_1358del | p.Glu452ThrfsTer8 | frameshift_variant | 8/9 | ENST00000373960.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DES | ENST00000373960.4 | c.1354_1358del | p.Glu452ThrfsTer8 | frameshift_variant | 8/9 | 1 | NM_001927.4 | P1 | |
ENST00000431827.1 | n.104+350_104+354del | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Desmin-related myofibrillar myopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 22, 2018 | This sequence change results in a premature translational stop signal in the DES gene (p.Glu452Thrfs*8). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 19 amino acids of the DES protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with DES-related disease. ClinVar contains an entry for this variant (Variation ID: 411148). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in DES cause disease. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at