2-219420551-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001927.4(DES):c.792C>T(p.Asp264Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00124 in 1,613,928 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0017 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 44 hom. )

Consequence

DES
NM_001927.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:20

Conservation

PhyloP100: 0.359

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.3).

BP6

Variant 2-219420551-C-T is Benign according to our data. Variant chr2-219420551-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 44271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-219420551-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 44271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-219420551-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 44271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-219420551-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 44271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-219420551-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 44271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-219420551-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 44271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-219420551-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 44271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-219420551-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 44271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-219420551-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 44271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-219420551-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 44271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-219420551-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 44271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-219420551-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 44271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-219420551-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 44271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-219420551-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 44271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-219420551-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 44271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-219420551-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 44271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-219420551-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 44271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-219420551-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 44271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-219420551-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 44271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-219420551-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 44271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-219420551-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 44271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-219420551-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 44271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-219420551-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 44271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-219420551-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 44271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-219420551-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 44271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-219420551-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 44271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-219420551-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 44271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-219420551-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 44271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-219420551-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 44271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-219420551-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 44271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-219420551-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 44271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-219420551-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 44271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-219420551-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 44271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-219420551-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 44271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-219420551-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 44271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-219420551-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 44271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-219420551-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 44271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-219420551-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 44271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.359 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00172 (262/152200) while in subpopulation AMR AF = 0.0137 (210/15290). AF 95% confidence interval is 0.0122. There are 4 homozygotes in GnomAd4. There are 142 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 4 AD,AR,SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DES	NM_001927.4 link	c.792C>T	p.Asp264Asp	synonymous_variant	Exon 4 of 9	ENST00000373960.4	NP_001918.3	P17661Q53SB5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DES	ENST00000373960.4 link	c.792C>T	p.Asp264Asp	synonymous_variant	Exon 4 of 9	1	NM_001927.4	ENSP00000363071.3	P17661
DES	ENST00000477226.6 link	n.266C>T		non_coding_transcript_exon_variant	Exon 3 of 8	4
DES	ENST00000492726.1 link	n.187C>T		non_coding_transcript_exon_variant	Exon 3 of 6	4
DES	ENST00000683013.1 link	n.180C>T		non_coding_transcript_exon_variant	Exon 2 of 7

Frequencies

GnomAD3 genomes

AF:

0.00172

AC:

262

AN:

152082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000773

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0138

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000480

GnomAD2 exomes

AF:

0.00526

AC:

1311

AN:

249380

AF XY:

0.00376

show subpopulations

Gnomad AFR exome

AF:

0.000868

Gnomad AMR exome

AF:

0.0361

Gnomad ASJ exome

AF:

0.000900

Gnomad EAS exome

AF:

0.000925

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000625

Gnomad OTH exome

AF:

0.00263

GnomAD4 exome

AF:

0.00119

AC:

1746

AN:

1461728

Hom.:

Cov.:

AF XY:

0.000974

AC XY:

708

AN XY:

727152

show subpopulations

African (AFR)

AF:

0.000358

AC:

AN:

33478

American (AMR)

AF:

0.0330

AC:

1475

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.000421

AC:

AN:

26136

East Asian (EAS)

AF:

0.000630

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53298

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000132

AC:

147

AN:

1111984

Other (OTH)

AF:

0.00119

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

147

294

440

587

734

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<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:

0.00172

AC:

262

AN:

152200

Hom.:

Cov.:

AF XY:

0.00191

AC XY:

142

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.000770

AC:

AN:

41532

American (AMR)

AF:

0.0137

AC:

210

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3472

East Asian (EAS)

AF:

0.00117

AC:

AN:

5150

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68020

Other (OTH)

AF:

0.000475

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.000700

Hom.:

Bravo

AF:

0.00351

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:20

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:8

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 22, 2020

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Apr 09, 2025

Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

May 05, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 25, 2019

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 17, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Asp264Asp in exon 4 of DES: This variant is not expected to have clinical signif icance because it does not change an amino acid and has been identified in 7/128 Mexican American chromosomes by the 1000 Genomes Project (dbSNP rs150370918). -

not provided

Benign:4

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 01, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Desmin-related myofibrillar myopathy

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Dilated cardiomyopathy 1I

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Myofibrillar Myopathy, Dominant

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Neurogenic scapuloperoneal syndrome, Kaeser type

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Cardiomyopathy

Benign:1

May 16, 2023

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

Benign:1

Sep 01, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cardiovascular phenotype

Benign:1

Feb 17, 2017

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as 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

-0.30

CADD

Benign

(source)

DANN

Benign

0.85

PhyloP100

0.36

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over