rs1058261

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001927.4(DES):c.828C>T(p.Asp276Asp) variant causes a synonymous change. The variant allele was found at a frequency of 0.344 in 1,613,578 control chromosomes in the GnomAD database, including 97,279 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10400 hom., cov: 31)

Exomes 𝑓: 0.34 ( 86879 hom. )

Consequence

DES
NM_001927.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:19

Conservation

PhyloP100: 4.17

Publications

26 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
myofibrillar myopathy
Inheritance: SD Classification: DEFINITIVE Submitted by: ClinGen
myofibrillar myopathy 1
Inheritance: SD, AD, AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
atrioventricular block
Inheritance: AR, AD 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

DES links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.26).

BP6

Variant 2-219420587-C-T is Benign according to our data. Variant chr2-219420587-C-T is described in ClinVar as Benign. ClinVar VariationId is 44272.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001927.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DES	NM_001927.4	MANE Select	c.828C>T	p.Asp276Asp	synonymous	Exon 4 of 9	NP_001918.3
DES	NM_001382708.1		c.825C>T	p.Asp275Asp	synonymous	Exon 4 of 9	NP_001369637.1
DES	NM_001382712.1		c.828C>T	p.Asp276Asp	synonymous	Exon 4 of 9	NP_001369641.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DES	ENST00000373960.4	TSL:1 MANE Select	c.828C>T	p.Asp276Asp	synonymous	Exon 4 of 9	ENSP00000363071.3	P17661
DES	ENST00000942906.1		c.828C>T	p.Asp276Asp	synonymous	Exon 4 of 10	ENSP00000612965.1
DES	ENST00000942898.1		c.828C>T	p.Asp276Asp	synonymous	Exon 4 of 9	ENSP00000612957.1

Frequencies

GnomAD3 genomes

AF:

0.363

AC:

55129

AN:

151730

Hom.:

10380

Cov.:

show subpopulations

Gnomad AFR

AF:

0.436

Gnomad AMI

AF:

0.438

Gnomad AMR

AF:

0.363

Gnomad ASJ

AF:

0.411

Gnomad EAS

AF:

0.184

Gnomad SAS

AF:

0.297

Gnomad FIN

AF:

0.265

Gnomad MID

AF:

0.418

Gnomad NFE

AF:

0.348

Gnomad OTH

AF:

0.380

GnomAD2 exomes

AF:

0.332

AC:

83064

AN:

250232

AF XY:

0.332

show subpopulations

Gnomad AFR exome

AF:

0.441

Gnomad AMR exome

AF:

0.310

Gnomad ASJ exome

AF:

0.421

Gnomad EAS exome

AF:

0.190

Gnomad FIN exome

AF:

0.280

Gnomad NFE exome

AF:

0.356

Gnomad OTH exome

AF:

0.358

GnomAD4 exome

AF:

0.342

AC:

499604

AN:

1461730

Hom.:

86879

Cov.:

AF XY:

0.341

AC XY:

247827

AN XY:

727172

show subpopulations

African (AFR)

AF:

0.443

AC:

14821

AN:

33478

American (AMR)

AF:

0.316

AC:

14133

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.415

AC:

10856

AN:

26136

East Asian (EAS)

AF:

0.183

AC:

7283

AN:

39698

South Asian (SAS)

AF:

0.296

AC:

25505

AN:

86252

European-Finnish (FIN)

AF:

0.276

AC:

14741

AN:

53360

Middle Eastern (MID)

AF:

0.428

AC:

2471

AN:

5768

European-Non Finnish (NFE)

AF:

0.349

AC:

388565

AN:

1111924

Other (OTH)

AF:

0.351

AC:

21229

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

22368

44737

67105

89474

111842

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12312

24624

36936

49248

61560

<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

AF:

0.363

AC:

55183

AN:

151848

Hom.:

10400

Cov.:

AF XY:

0.360

AC XY:

26709

AN XY:

74200

show subpopulations

African (AFR)

AF:

0.436

AC:

18052

AN:

41370

American (AMR)

AF:

0.363

AC:

5530

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.411

AC:

1427

AN:

3468

East Asian (EAS)

AF:

0.184

AC:

946

AN:

5146

South Asian (SAS)

AF:

0.296

AC:

1426

AN:

4824

European-Finnish (FIN)

AF:

0.265

AC:

2796

AN:

10544

Middle Eastern (MID)

AF:

0.422

AC:

124

AN:

294

European-Non Finnish (NFE)

AF:

0.348

AC:

23667

AN:

67936

Other (OTH)

AF:

0.387

AC:

816

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1749

3497

5246

6994

8743

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

512

1024

1536

2048

2560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.361

Hom.:

45448

Bravo

AF:

0.375

Asia WGS

AF:

0.286

AC:

996

AN:

3478

EpiCase

AF:

0.366

EpiControl

AF:

0.361

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (11)

Desmin-related myofibrillar myopathy (2)

not provided (2)

Cardiovascular phenotype (1)

Dilated cardiomyopathy 1I (1)

Myofibrillar Myopathy, Dominant (1)

Neurogenic scapuloperoneal syndrome, Kaeser type (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Benign

0.89

PhyloP100

4.2

Mutation Taster

=83/17

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over