chr2-219418456-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS1

The NM_001927.4(DES):c.-7C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000265 in 1,581,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

DES
NM_001927.4 5_prime_UTR

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:1

Conservation

PhyloP100: 1.32

Publications

0 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 -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 2-219418456-C-G is Benign according to our data. Variant chr2-219418456-C-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 290155.

BS1

Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.0000279 (40/1431366) while in subpopulation AMR AF = 0.000715 (31/43330). AF 95% confidence interval is 0.000517. There are 0 homozygotes in GnomAdExome4. There are 18 alleles in the male GnomAdExome4 subpopulation. Median coverage is 29. This position passed quality control check.

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.-7C>G	5_prime_UTR	Exon 1 of 9	NP_001918.3
DES	NM_001382708.1		c.-7C>G	5_prime_UTR	Exon 1 of 9	NP_001369637.1
DES	NM_001382712.1		c.-7C>G	5_prime_UTR	Exon 1 of 9	NP_001369641.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DES	ENST00000373960.4	TSL:1 MANE Select	c.-7C>G	5_prime_UTR	Exon 1 of 9	ENSP00000363071.3	P17661
DES	ENST00000942906.1		c.-7C>G	5_prime_UTR	Exon 1 of 10	ENSP00000612965.1
DES	ENST00000942898.1		c.-7C>G	5_prime_UTR	Exon 1 of 9	ENSP00000612957.1

Frequencies

GnomAD3 genomes

AF:

0.0000133

AC:

AN:

150572

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000170

AC:

AN:

205878

AF XY:

0.000121

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000774

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000108

Gnomad OTH exome

AF:

0.00175

GnomAD4 exome

AF:

0.0000279

AC:

AN:

1431366

Hom.:

Cov.:

AF XY:

0.0000253

AC XY:

AN XY:

711958

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30720

American (AMR)

AF:

0.000715

AC:

AN:

43330

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25426

East Asian (EAS)

AF:

0.00

AC:

AN:

37464

South Asian (SAS)

AF:

0.00

AC:

AN:

83914

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41958

Middle Eastern (MID)

AF:

0.000669

AC:

AN:

4486

European-Non Finnish (NFE)

AF:

0.00000181

AC:

AN:

1104786

Other (OTH)

AF:

0.0000675

AC:

AN:

59282

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000133

AC:

AN:

150572

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73596

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

39940

American (AMR)

AF:

0.000131

AC:

AN:

15220

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000435

Hom.:

Bravo

AF:

0.0000453

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Dilated cardiomyopathy 1I (1)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Benign

0.90

PhyloP100

1.3

PromoterAI

-0.15

Neutral

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over