rs2293668

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_004006.3(DMD):c.9649+15T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.84 ( 27532 hom., 27775 hem., cov: 23)

Exomes 𝑓: 0.87 ( 279734 hom. 299840 hem. )

Failed GnomAD Quality Control

Consequence

DMD
NM_004006.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:15

Conservation

PhyloP100: 0.472

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, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
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

new If you want to explore the variant's impact on the transcript NM_004006.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant X-31206567-A-G is Benign according to our data. Variant chrX-31206567-A-G is described in ClinVar as Benign. ClinVar VariationId is 94854.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.9649+15T>C	intron	N/A	NP_003997.2	P11532-1
DMD	NM_004009.3		c.9637+15T>C	intron	N/A	NP_004000.1	P11532
DMD	NM_000109.4		c.9625+15T>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.9649+15T>C	intron	N/A	ENSP00000354923.3	P11532-1
DMD	ENST00000378723.7	TSL:1	c.445+15T>C	intron	N/A	ENSP00000367997.3	P11532-6
DMD	ENST00000361471.8	TSL:1	c.445+15T>C	intron	N/A	ENSP00000354464.4	P11532-5

Frequencies

GnomAD3 genomes

AF:

0.840

AC:

92965

AN:

110693

Hom.:

27535

Cov.:

show subpopulations

Gnomad AFR

AF:

0.734

Gnomad AMI

AF:

0.913

Gnomad AMR

AF:

0.908

Gnomad ASJ

AF:

0.863

Gnomad EAS

AF:

0.803

Gnomad SAS

AF:

0.819

Gnomad FIN

AF:

0.888

Gnomad MID

AF:

0.878

Gnomad NFE

AF:

0.883

Gnomad OTH

AF:

0.859

GnomAD2 exomes

AF:

0.867

AC:

148595

AN:

171412

AF XY:

0.870

show subpopulations

Gnomad AFR exome

AF:

0.737

Gnomad AMR exome

AF:

0.922

Gnomad ASJ exome

AF:

0.862

Gnomad EAS exome

AF:

0.802

Gnomad FIN exome

AF:

0.883

Gnomad NFE exome

AF:

0.884

Gnomad OTH exome

AF:

0.887

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.874

AC:

938413

AN:

1073286

Hom.:

279734

Cov.:

AF XY:

0.874

AC XY:

299840

AN XY:

343168

show subpopulations

African (AFR)

AF:

0.730

AC:

18921

AN:

25908

American (AMR)

AF:

0.921

AC:

32139

AN:

34912

Ashkenazi Jewish (ASJ)

AF:

0.859

AC:

16477

AN:

19188

East Asian (EAS)

AF:

0.815

AC:

24446

AN:

30001

South Asian (SAS)

AF:

0.835

AC:

44081

AN:

52820

European-Finnish (FIN)

AF:

0.879

AC:

35437

AN:

40324

Middle Eastern (MID)

AF:

0.852

AC:

3465

AN:

4067

European-Non Finnish (NFE)

AF:

0.883

AC:

724314

AN:

820742

Other (OTH)

AF:

0.863

AC:

39133

AN:

45324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

3921

7843

11764

15686

19607

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19406

38812

58218

77624

97030

<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

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.840

AC:

93027

AN:

110750

Hom.:

27532

Cov.:

AF XY:

0.843

AC XY:

27775

AN XY:

32960

show subpopulations

African (AFR)

AF:

0.734

AC:

22375

AN:

30492

American (AMR)

AF:

0.908

AC:

9463

AN:

10418

Ashkenazi Jewish (ASJ)

AF:

0.863

AC:

2279

AN:

2640

East Asian (EAS)

AF:

0.804

AC:

2816

AN:

3504

South Asian (SAS)

AF:

0.819

AC:

2128

AN:

2597

European-Finnish (FIN)

AF:

0.888

AC:

5192

AN:

5849

Middle Eastern (MID)

AF:

0.880

AC:

191

AN:

217

European-Non Finnish (NFE)

AF:

0.883

AC:

46665

AN:

52846

Other (OTH)

AF:

0.861

AC:

1302

AN:

1512

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

526

1053

1579

2106

2632

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

772

1544

2316

3088

3860

<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:

0.865

Hom.:

152131

Bravo

AF:

0.839

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (8)

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

-0.53

CADD

Benign

5.6

(source)

DANN

Benign

0.76

PhyloP100

0.47

PromoterAI

-0.0042

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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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