chr2-219420057-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001927.4(DES):c.579-38C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 1,612,128 control chromosomes in the GnomAD database, including 323,996 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.51 ( 23854 hom., cov: 32)

Exomes 𝑓: 0.63 ( 300142 hom. )

Consequence

DES
NM_001927.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.356

Publications

9 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 -20 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 1 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 2-219420057-C-T is Benign according to our data. Variant chr2-219420057-C-T is described in ClinVar as Benign. ClinVar VariationId is 258491.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.794 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	Effect	Exon Rank	Protein
DES	NM_001927.4	MANE Select	c.579-38C>T	intron	N/A	NP_001918.3
DES	NM_001382708.1		c.579-38C>T	intron	N/A	NP_001369637.1
DES	NM_001382712.1		c.579-38C>T	intron	N/A	NP_001369641.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DES	ENST00000373960.4	TSL:1 MANE Select	c.579-38C>T	intron	N/A	ENSP00000363071.3	P17661
DES	ENST00000942906.1		c.579-38C>T	intron	N/A	ENSP00000612965.1
DES	ENST00000942898.1		c.579-38C>T	intron	N/A	ENSP00000612957.1

Frequencies

GnomAD3 genomes

AF:

0.514

AC:

78131

AN:

151906

Hom.:

23852

Cov.:

show subpopulations

Gnomad AFR

AF:

0.166

Gnomad AMI

AF:

0.563

Gnomad AMR

AF:

0.586

Gnomad ASJ

AF:

0.563

Gnomad EAS

AF:

0.814

Gnomad SAS

AF:

0.677

Gnomad FIN

AF:

0.732

Gnomad MID

AF:

0.529

Gnomad NFE

AF:

0.639

Gnomad OTH

AF:

0.525

GnomAD2 exomes

AF:

0.627

AC:

157680

AN:

251340

AF XY:

0.634

show subpopulations

Gnomad AFR exome

AF:

0.156

Gnomad AMR exome

AF:

0.664

Gnomad ASJ exome

AF:

0.560

Gnomad EAS exome

AF:

0.809

Gnomad FIN exome

AF:

0.718

Gnomad NFE exome

AF:

0.631

Gnomad OTH exome

AF:

0.613

GnomAD4 exome

AF:

0.635

AC:

927141

AN:

1460104

Hom.:

300142

Cov.:

AF XY:

0.637

AC XY:

462738

AN XY:

726482

show subpopulations

African (AFR)

AF:

0.146

AC:

4895

AN:

33424

American (AMR)

AF:

0.656

AC:

29340

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.564

AC:

14729

AN:

26128

East Asian (EAS)

AF:

0.816

AC:

32404

AN:

39692

South Asian (SAS)

AF:

0.677

AC:

58339

AN:

86232

European-Finnish (FIN)

AF:

0.721

AC:

38505

AN:

53392

Middle Eastern (MID)

AF:

0.527

AC:

3014

AN:

5720

European-Non Finnish (NFE)

AF:

0.639

AC:

709219

AN:

1110464

Other (OTH)

AF:

0.608

AC:

36696

AN:

60336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

19861

39722

59583

79444

99305

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18724

37448

56172

74896

93620

<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:

0.514

AC:

78127

AN:

152024

Hom.:

23854

Cov.:

AF XY:

0.521

AC XY:

38719

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.165

AC:

6851

AN:

41454

American (AMR)

AF:

0.586

AC:

8954

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.563

AC:

1953

AN:

3470

East Asian (EAS)

AF:

0.814

AC:

4191

AN:

5148

South Asian (SAS)

AF:

0.678

AC:

3270

AN:

4820

European-Finnish (FIN)

AF:

0.732

AC:

7746

AN:

10584

Middle Eastern (MID)

AF:

0.521

AC:

152

AN:

292

European-Non Finnish (NFE)

AF:

0.639

AC:

43403

AN:

67958

Other (OTH)

AF:

0.518

AC:

1096

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1587

3175

4762

6350

7937

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

680

1360

2040

2720

3400

<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:

0.572

Hom.:

8650

Bravo

AF:

0.488

Asia WGS

AF:

0.672

AC:

2337

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Desmin-related myofibrillar myopathy (1)

Dilated cardiomyopathy 1I (1)

Neurogenic scapuloperoneal syndrome, Kaeser type (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

6.6

(source)

DANN

Benign

0.71

PhyloP100

-0.36

BranchPoint Hunter

1.0

Mutation Taster

=100/0

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

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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