dbSNP rs151226355: DES:c.735+20C>T (chr2-219420366-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001927.4(DES):c.735+20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00911 in 1,613,330 control chromosomes in the GnomAD database, including 108 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0072 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0093 ( 103 hom. )

Consequence

DES
NM_001927.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:12

Conservation

PhyloP100: -0.194

Publications

4 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

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 2-219420366-C-T is Benign according to our data. Variant chr2-219420366-C-T is described in ClinVar as Benign. ClinVar VariationId is 44269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00717 (1091/152254) while in subpopulation NFE AF = 0.0104 (705/68024). AF 95% confidence interval is 0.00973. There are 5 homozygotes in GnomAd4. There are 562 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 5 SD,AR,AD gene

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.735+20C>T	intron	N/A	NP_001918.3
DES	NM_001382708.1		c.732+20C>T	intron	N/A	NP_001369637.1
DES	NM_001382712.1		c.735+20C>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.735+20C>T	intron	N/A	ENSP00000363071.3	P17661
DES	ENST00000942906.1		c.735+20C>T	intron	N/A	ENSP00000612965.1
DES	ENST00000942898.1		c.735+20C>T	intron	N/A	ENSP00000612957.1

Frequencies

GnomAD3 genomes

AF:

0.00717

AC:

1091

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00159

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0100

Gnomad ASJ

AF:

0.0156

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00830

Gnomad FIN

AF:

0.00273

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0104

Gnomad OTH

AF:

0.0129

GnomAD2 exomes

AF:

0.00896

AC:

2245

AN:

250566

AF XY:

0.00967

show subpopulations

Gnomad AFR exome

AF:

0.00130

Gnomad AMR exome

AF:

0.00615

Gnomad ASJ exome

AF:

0.0171

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00380

Gnomad NFE exome

AF:

0.0125

Gnomad OTH exome

AF:

0.0137

GnomAD4 exome

AF:

0.00931

AC:

13602

AN:

1461076

Hom.:

103

Cov.:

AF XY:

0.00950

AC XY:

6904

AN XY:

726874

show subpopulations

African (AFR)

AF:

0.00218

AC:

AN:

33466

American (AMR)

AF:

0.00680

AC:

304

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.0184

AC:

482

AN:

26134

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39690

South Asian (SAS)

AF:

0.00798

AC:

688

AN:

86206

European-Finnish (FIN)

AF:

0.00378

AC:

201

AN:

53110

Middle Eastern (MID)

AF:

0.0392

AC:

225

AN:

5738

European-Non Finnish (NFE)

AF:

0.00990

AC:

11003

AN:

1111672

Other (OTH)

AF:

0.0104

AC:

625

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

790

1581

2371

3162

3952

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

374

748

1122

1496

1870

<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:

0.00717

AC:

1091

AN:

152254

Hom.:

Cov.:

AF XY:

0.00755

AC XY:

562

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.00161

AC:

AN:

41546

American (AMR)

AF:

0.0100

AC:

153

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0156

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00830

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00273

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0104

AC:

705

AN:

68024

Other (OTH)

AF:

0.0128

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

105

158

210

263

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00991

Hom.:

Bravo

AF:

0.00739

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (7)

not provided (4)

Desmin-related myofibrillar myopathy (1)

Myofibrillar myopathy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

3.3

(source)

DANN

Benign

0.70

PhyloP100

-0.19

Mutation Taster

=100/0

polymorphism

(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