GeneBe

rs1262196309

Variant names:

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7

The NM_001927.4(DES):​c.9G>A​(p.Gln3Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000277 in 1,444,030 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

DES
NM_001927.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.80

Publications

1 publications found
Variant links:
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 cardiomyopathy
    Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
  • dilated cardiomyopathy 1I
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
  • myofibrillar myopathy 1
    Inheritance: AD, AR, SD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
  • atrioventricular block
    Inheritance: AD, AR Classification: STRONG Submitted by: Genomics England PanelApp
  • arrhythmogenic right ventricular cardiomyopathy
    Inheritance: AD Classification: MODERATE Submitted by: ClinGen
  • familial isolated dilated cardiomyopathy
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • neurogenic scapuloperoneal syndrome, Kaeser type
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
Variant 2-219418471-G-A is Benign according to our data. Variant chr2-219418471-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1768930.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=2.8 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DESNM_001927.4 linkc.9G>A p.Gln3Gln synonymous_variant Exon 1 of 9 ENST00000373960.4 NP_001918.3 P17661Q53SB5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DESENST00000373960.4 linkc.9G>A p.Gln3Gln synonymous_variant Exon 1 of 9 1 NM_001927.4 ENSP00000363071.3 P17661

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000277
AC:
4
AN:
1444030
Hom.:
0
Cov.:
29
AF XY:
0.00000557
AC XY:
4
AN XY:
718640
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
32288
American (AMR)
AF:
0.00
AC:
0
AN:
44220
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25752
East Asian (EAS)
AF:
0.00
AC:
0
AN:
38614
South Asian (SAS)
AF:
0.00
AC:
0
AN:
85284
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
44454
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4922
European-Non Finnish (NFE)
AF:
0.00000361
AC:
4
AN:
1108746
Other (OTH)
AF:
0.00
AC:
0
AN:
59750
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Desmin-related myofibrillar myopathy Benign:1
Apr 11, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Cardiovascular phenotype Benign:1
Aug 16, 2019
Ambry Genetics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.54
CADD
Benign
15
DANN
Benign
0.97
PhyloP100
2.8
PromoterAI
-0.079
Neutral
Mutation Taster
=78/22
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs1262196309; hg19: chr2-220283193; API