rs228373

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004006.3(DMD):c.2168+13T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 1,203,283 control chromosomes in the GnomAD database, including 31,458 homozygotes. There are 103,963 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 4627 hom., 10534 hem., cov: 23)

Exomes 𝑓: 0.26 ( 26831 hom. 93429 hem. )

Consequence

DMD
NM_004006.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:14

Conservation

PhyloP100: 0.890

Publications

11 publications found

Variant links:

Genes affected

DMD (HGNC:2928): (dystrophin) This gene spans a genomic range of greater than 2 Mb and encodes a large protein containing an N-terminal actin-binding domain and multiple spectrin repeats. The encoded protein forms a component of the dystrophin-glycoprotein complex (DGC), which bridges the inner cytoskeleton and the extracellular matrix. Deletions, duplications, and point mutations at this gene locus may cause Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), or cardiomyopathy. Alternative promoter usage and alternative splicing result in numerous distinct transcript variants and protein isoforms for this gene. [provided by RefSeq, Dec 2016]

DMD Gene-Disease associations (from GenCC):

Becker muscular dystrophy
Inheritance: XL Classification: DEFINITIVE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet
dilated cardiomyopathy 3B
Inheritance: XL Classification: DEFINITIVE Submitted by: Ambry Genetics
Duchenne and Becker muscular dystrophy
Inheritance: XL Classification: DEFINITIVE Submitted by: Myriad Women’s Health
Duchenne muscular dystrophy
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
progressive muscular dystrophy
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
familial isolated dilated cardiomyopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
non-syndromic X-linked intellectual disability
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
symptomatic form of muscular dystrophy of Duchenne and Becker in female carriers
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

DMD 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=-0.83).

BP6

Variant X-32545146-A-G is Benign according to our data. Variant chrX-32545146-A-G is described in ClinVar as Benign. ClinVar VariationId is 94495.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004006.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DMD	NM_004006.3	MANE Select	c.2168+13T>C	intron	N/A	NP_003997.2	P11532-1
DMD	NM_004009.3		c.2156+13T>C	intron	N/A	NP_004000.1	P11532
DMD	NM_000109.4		c.2144+13T>C	intron	N/A	NP_000100.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DMD	ENST00000357033.9	TSL:1 MANE Select	c.2168+13T>C	intron	N/A	ENSP00000354923.3	P11532-1
DMD	ENST00000288447.9	TSL:1	c.2144+13T>C	intron	N/A	ENSP00000288447.4	Q4G0X0
DMD	ENST00000378677.6	TSL:5	c.2156+13T>C	intron	N/A	ENSP00000367948.2	P11532-11

Frequencies

GnomAD3 genomes

AF:

0.323

AC:

35839

AN:

111110

Hom.:

4620

Cov.:

show subpopulations

Gnomad AFR

AF:

0.468

Gnomad AMI

AF:

0.151

Gnomad AMR

AF:

0.337

Gnomad ASJ

AF:

0.272

Gnomad EAS

AF:

0.545

Gnomad SAS

AF:

0.315

Gnomad FIN

AF:

0.262

Gnomad MID

AF:

0.264

Gnomad NFE

AF:

0.234

Gnomad OTH

AF:

0.320

GnomAD2 exomes

AF:

0.313

AC:

56257

AN:

180013

AF XY:

0.299

show subpopulations

Gnomad AFR exome

AF:

0.474

Gnomad AMR exome

AF:

0.397

Gnomad ASJ exome

AF:

0.273

Gnomad EAS exome

AF:

0.537

Gnomad FIN exome

AF:

0.279

Gnomad NFE exome

AF:

0.232

Gnomad OTH exome

AF:

0.289

GnomAD4 exome

AF:

0.260

AC:

284460

AN:

1092120

Hom.:

26831

Cov.:

AF XY:

0.261

AC XY:

93429

AN XY:

358552

show subpopulations

African (AFR)

AF:

0.475

AC:

12472

AN:

26258

American (AMR)

AF:

0.394

AC:

13785

AN:

35018

Ashkenazi Jewish (ASJ)

AF:

0.269

AC:

5206

AN:

19328

East Asian (EAS)

AF:

0.523

AC:

15768

AN:

30133

South Asian (SAS)

AF:

0.304

AC:

16428

AN:

53962

European-Finnish (FIN)

AF:

0.278

AC:

11250

AN:

40420

Middle Eastern (MID)

AF:

0.345

AC:

1380

AN:

3998

European-Non Finnish (NFE)

AF:

0.233

AC:

195283

AN:

837162

Other (OTH)

AF:

0.281

AC:

12888

AN:

45841

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

6529

13059

19588

26118

32647

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7322

14644

21966

29288

36610

<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:

0.323

AC:

35881

AN:

111163

Hom.:

4627

Cov.:

AF XY:

0.315

AC XY:

10534

AN XY:

33449

show subpopulations

African (AFR)

AF:

0.468

AC:

14277

AN:

30530

American (AMR)

AF:

0.338

AC:

3533

AN:

10464

Ashkenazi Jewish (ASJ)

AF:

0.272

AC:

716

AN:

2637

East Asian (EAS)

AF:

0.547

AC:

1894

AN:

3463

South Asian (SAS)

AF:

0.313

AC:

840

AN:

2680

European-Finnish (FIN)

AF:

0.262

AC:

1570

AN:

5998

Middle Eastern (MID)

AF:

0.243

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.234

AC:

12397

AN:

52969

Other (OTH)

AF:

0.327

AC:

498

AN:

1521

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

856

1712

2567

3423

4279

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

362

724

1086

1448

1810

<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:

0.276

Hom.:

32020

Bravo

AF:

0.342

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (7)

Dilated cardiomyopathy 3B (2)

Duchenne muscular dystrophy (2)

not provided (2)

Duchenne muscular dystrophy;C0878544:Cardiomyopathy;C0917713:Becker muscular dystrophy;na:Dystrophin deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

(source)

DANN

Benign

0.78

PhyloP100

0.89

Mutation Taster

=100/0

polymorphism (auto)

(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

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