2-219420057-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -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

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

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 id is 258491.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-219420057-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DES	NM_001927.4 link	c.579-38C>T		intron_variant	Intron 1 of 8	ENST00000373960.4	NP_001918.3	P17661Q53SB5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
DES	ENST00000373960.4 link	c.579-38C>T	intron_variant	Intron 1 of 8	1	NM_001927.4	ENSP00000363071.3	P17661
DES	ENST00000477226.6 link	n.15C>T	non_coding_transcript_exon_variant	Exon 1 of 8	4
DES	ENST00000492726.1 link	n.-65C>T	upstream_gene_variant		4
DES	ENST00000683013.1 link	n.-167C>T	upstream_gene_variant

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

GnomAD3 exomes

AF:

0.627

AC:

157680

AN:

251340

Hom.:

51802

AF XY:

0.634

AC XY:

86112

AN XY:

135838

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 SAS exome

AF:

0.675

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

Gnomad4 AFR exome

AF:

0.146

Gnomad4 AMR exome

AF:

0.656

Gnomad4 ASJ exome

AF:

0.564

Gnomad4 EAS exome

AF:

0.816

Gnomad4 SAS exome

AF:

0.677

Gnomad4 FIN exome

AF:

0.721

Gnomad4 NFE exome

AF:

0.639

Gnomad4 OTH exome

AF:

0.608

GnomAD4 genome

AF:

0.514

AC:

78127

AN:

152024

Hom.:

23854

Cov.:

AF XY:

0.521

AC XY:

38719

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.165

Gnomad4 AMR

AF:

0.586

Gnomad4 ASJ

AF:

0.563

Gnomad4 EAS

AF:

0.814

Gnomad4 SAS

AF:

0.678

Gnomad4 FIN

AF:

0.732

Gnomad4 NFE

AF:

0.639

Gnomad4 OTH

AF:

0.518

Alfa

AF:

0.571

Hom.:

4961

Bravo

AF:

0.488

Asia WGS

AF:

0.672

AC:

2337

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 13, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Desmin-related myofibrillar myopathy

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dilated cardiomyopathy 1I

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Neurogenic scapuloperoneal syndrome, Kaeser type

Benign:1

Jul 30, 2021

Genome-Nilou Lab

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

-0.80

CADD

Benign

6.6

DANN

Benign

0.71

BranchPoint Hunter

1.0

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