2-219418477-C-G
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1PM2
The NM_001927.4(DES):c.15C>G(p.Tyr5*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,445,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
DES
NM_001927.4 stop_gained
NM_001927.4 stop_gained
Scores
2
4
1
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.59
Publications
0 publications found
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]
DES Gene-Disease associations (from GenCC):
- dilated cardiomyopathyInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- dilated cardiomyopathy 1IInheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
- myofibrillar myopathy 1Inheritance: AD, AR, SD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
- atrioventricular blockInheritance: AD, AR Classification: STRONG Submitted by: Genomics England PanelApp
- arrhythmogenic right ventricular cardiomyopathyInheritance: AD Classification: MODERATE Submitted by: ClinGen
- familial isolated dilated cardiomyopathyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- neurogenic scapuloperoneal syndrome, Kaeser typeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 10 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 126 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 6.92e-7 AC: 1AN: 1445662Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 719462 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1445662
Hom.:
Cov.:
29
AF XY:
AC XY:
0
AN XY:
719462
show subpopulations
African (AFR)
AF:
AC:
0
AN:
32326
American (AMR)
AF:
AC:
0
AN:
44228
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25786
East Asian (EAS)
AF:
AC:
0
AN:
38630
South Asian (SAS)
AF:
AC:
0
AN:
85358
European-Finnish (FIN)
AF:
AC:
0
AN:
45578
Middle Eastern (MID)
AF:
AC:
0
AN:
5064
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1108920
Other (OTH)
AF:
AC:
0
AN:
59772
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
PhyloP100
Vest4
GERP RS
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
Publications
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