rs151226355

Variant names:

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 44269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-219420366-C-T is described in Lovd as [Benign]. Variant chr2-219420366-C-T is described in Lovd as [Likely_benign].

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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DES	NM_001927.4 link	c.735+20C>T		intron_variant	Intron 3 of 8	ENST00000373960.4	NP_001918.3	P17661Q53SB5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
DES	ENST00000373960.4 link	c.735+20C>T	intron_variant	Intron 3 of 8	1	NM_001927.4	ENSP00000363071.3	P17661
DES	ENST00000477226.6 link	n.209+20C>T	intron_variant	Intron 2 of 7	4
DES	ENST00000492726.1 link	n.130+20C>T	intron_variant	Intron 2 of 5	4
DES	ENST00000683013.1 link	n.123+20C>T	intron_variant	Intron 1 of 6

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

GnomAD3 exomes

AF:

0.00896

AC:

2245

AN:

250566

Hom.:

AF XY:

0.00967

AC XY:

1310

AN XY:

135432

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 SAS exome

AF:

0.00844

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

Gnomad4 AFR exome

AF:

0.00218

Gnomad4 AMR exome

AF:

0.00680

Gnomad4 ASJ exome

AF:

0.0184

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00798

Gnomad4 FIN exome

AF:

0.00378

Gnomad4 NFE exome

AF:

0.00990

Gnomad4 OTH exome

AF:

0.0104

GnomAD4 genome

AF:

0.00717

AC:

1091

AN:

152254

Hom.:

Cov.:

AF XY:

0.00755

AC XY:

562

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.00161

Gnomad4 AMR

AF:

0.0100

Gnomad4 ASJ

AF:

0.0156

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00830

Gnomad4 FIN

AF:

0.00273

Gnomad4 NFE

AF:

0.0104

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.0102

Hom.:

Bravo

AF:

0.00739

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

Mar 03, 2008

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

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: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

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

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:4

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 14, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Myofibrillar myopathy

Uncertain:1

Aug 16, 2016

Wellcome Centre for Mitochondrial Research, Newcastle University

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Desmin-related myofibrillar myopathy

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

3.3

DANN

Benign

0.70

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over