rs397516699

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The ENST00000373960.4(DES):c.897+3_897+4delGG variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 1,613,966 control chromosomes in the GnomAD database, including 39 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00047 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0011 ( 39 hom. )

Consequence

DES
ENST00000373960.4 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:18

Conservation

PhyloP100: 0.421

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

DES links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 2-219420658-TGG-T is Benign according to our data. Variant chr2-219420658-TGG-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 44273.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000473 (72/152142) while in subpopulation SAS AF = 0.0133 (64/4814). AF 95% confidence interval is 0.0107. There are 0 homozygotes in GnomAd4. There are 49 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 39 AD,AR,SD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000373960.4. 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.897+4_897+5delGG	splice_region intron	N/A	NP_001918.3
DES	NM_001382708.1		c.894+4_894+5delGG	splice_region intron	N/A	NP_001369637.1
DES	NM_001382712.1		c.897+4_897+5delGG	splice_region intron	N/A	NP_001369641.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
DES	ENST00000373960.4	TSL:1 MANE Select	c.897+3_897+4delGG	splice_region intron	N/A	ENSP00000363071.3
DES	ENST00000477226.6	TSL:4	n.371+3_371+4delGG	splice_region intron	N/A
DES	ENST00000492726.1	TSL:4	n.292+3_292+4delGG	splice_region intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000480

AC:

AN:

152024

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0135

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00210

AC:

528

AN:

251216

AF XY:

0.00297

show subpopulations

Gnomad AFR exome

AF:

0.0000617

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000881

Gnomad OTH exome

AF:

0.00130

GnomAD4 exome

AF:

0.00106

AC:

1553

AN:

1461824

Hom.:

AF XY:

0.00160

AC XY:

1162

AN XY:

727208

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.0000224

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000574

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39694

South Asian (SAS)

AF:

0.0161

AC:

1393

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53360

Middle Eastern (MID)

AF:

0.00537

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000585

AC:

AN:

1112010

Other (OTH)

AF:

0.000778

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

136

272

409

545

681

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.000473

AC:

AN:

152142

Hom.:

Cov.:

AF XY:

0.000659

AC XY:

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41518

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5154

South Asian (SAS)

AF:

0.0133

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

67990

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000477

Hom.:

Bravo

AF:

0.000113

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (5)

Desmin-related myofibrillar myopathy (3)

not provided (2)

Cardiomyopathy (1)

Cardiovascular phenotype (1)

DES-related disorder (1)

Desmin-related myofibrillar myopathy;C1858154:Dilated cardiomyopathy 1I;C1867005:Neurogenic scapuloperoneal syndrome, Kaeser type (1)

Dilated cardiomyopathy 1I (1)

Dilated Cardiomyopathy, Dominant (1)

Myofibrillar Myopathy, Dominant (1)

Scapuloperoneal weakness (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.42

Mutation Taster

=72/28

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over