NM_004006.3:c.8810G>A

Variant names:

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.8810G>A(p.Arg2937Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.94 ( 34549 hom., 29566 hem., cov: 21)

Exomes 𝑓: 0.92 ( 315558 hom. 332140 hem. )

Failed GnomAD Quality Control

Consequence

DMD
NM_004006.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 0.643

Publications

44 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Orphanet
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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.9673455E-6).

BP6

Variant X-31478233-C-T is Benign according to our data. Variant chrX-31478233-C-T is described in ClinVar as Benign. ClinVar VariationId is 166667.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMD	NM_004006.3 link	c.8810G>A	p.Arg2937Gln	missense_variant	Exon 59 of 79	ENST00000357033.9	NP_003997.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMD	ENST00000357033.9 link	c.8810G>A	p.Arg2937Gln	missense_variant	Exon 59 of 79	1	NM_004006.3	ENSP00000354923.3

Frequencies

GnomAD3 genomes

AF:

0.939

AC:

102725

AN:

109406

Hom.:

34555

Cov.:

show subpopulations

Gnomad AFR

AF:

0.986

Gnomad AMI

AF:

0.900

Gnomad AMR

AF:

0.859

Gnomad ASJ

AF:

0.977

Gnomad EAS

AF:

0.929

Gnomad SAS

AF:

0.680

Gnomad FIN

AF:

0.944

Gnomad MID

AF:

0.949

Gnomad NFE

AF:

0.938

Gnomad OTH

AF:

0.942

GnomAD2 exomes

AF:

0.898

AC:

164218

AN:

182910

AF XY:

0.890

show subpopulations

Gnomad AFR exome

AF:

0.990

Gnomad AMR exome

AF:

0.795

Gnomad ASJ exome

AF:

0.979

Gnomad EAS exome

AF:

0.922

Gnomad FIN exome

AF:

0.941

Gnomad NFE exome

AF:

0.941

Gnomad OTH exome

AF:

0.922

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.922

AC:

1012027

AN:

1098075

Hom.:

315558

Cov.:

AF XY:

0.914

AC XY:

332140

AN XY:

363441

show subpopulations

African (AFR)

AF:

0.990

AC:

26142

AN:

26402

American (AMR)

AF:

0.803

AC:

28212

AN:

35144

Ashkenazi Jewish (ASJ)

AF:

0.979

AC:

18978

AN:

19386

East Asian (EAS)

AF:

0.939

AC:

28345

AN:

30201

South Asian (SAS)

AF:

0.715

AC:

38719

AN:

54134

European-Finnish (FIN)

AF:

0.940

AC:

38080

AN:

40520

Middle Eastern (MID)

AF:

0.946

AC:

3914

AN:

4137

European-Non Finnish (NFE)

AF:

0.935

AC:

787144

AN:

842059

Other (OTH)

AF:

0.922

AC:

42493

AN:

46092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

3343

6686

10028

13371

16714

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20850

41700

62550

83400

104250

<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:

0.939

AC:

102770

AN:

109458

Hom.:

34549

Cov.:

AF XY:

0.933

AC XY:

29566

AN XY:

31678

show subpopulations

African (AFR)

AF:

0.986

AC:

29666

AN:

30074

American (AMR)

AF:

0.858

AC:

8725

AN:

10172

Ashkenazi Jewish (ASJ)

AF:

0.977

AC:

2562

AN:

2622

East Asian (EAS)

AF:

0.929

AC:

3200

AN:

3446

South Asian (SAS)

AF:

0.682

AC:

1683

AN:

2466

European-Finnish (FIN)

AF:

0.944

AC:

5372

AN:

5691

Middle Eastern (MID)

AF:

0.949

AC:

203

AN:

214

European-Non Finnish (NFE)

AF:

0.938

AC:

49357

AN:

52611

Other (OTH)

AF:

0.938

AC:

1393

AN:

1485

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

207

414

622

829

1036

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

798

1596

2394

3192

3990

<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:

0.937

Hom.:

123137

Bravo

AF:

0.937

TwinsUK

AF:

0.939

AC:

3481

ALSPAC

AF:

0.936

AC:

2704

ESP6500AA

AF:

0.988

AC:

3786

ESP6500EA

AF:

0.939

AC:

6319

ExAC

AF:

0.898

AC:

108988

EpiCase

AF:

0.942

EpiControl

AF:

0.940

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Feb 02, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Clinical Genetics, Academic Medical Center

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

Nov 26, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This is a RefSeq error. The reference base (c.8810G) is the minor allele. This a llele (G) has been identified in 6% (409/6728) of European American chromosomes and 1% (47/3833) of African American chromosomes by the NHLBI Exome Sequencing P roject (http://evs.gs.washington.edu/EVS/; dbSNP rs1800280) and thus meets crite ria to be classified as benign.

Duchenne muscular dystrophy

Benign:3

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:2

Nov 21, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

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

Benign:1

Apr 20, 2017

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Dilated cardiomyopathy 3B

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

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.82

CADD

Benign

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.0

.;T;T;T;.;.;T;.;.;T

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.66

T;.;.;.;.;T;.;T;T;.

MetaRNN

Benign

0.0000020

T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.0

.;.;.;.;.;.;.;.;.;.

PhyloP100

0.64

PrimateAI

Benign

0.37

PROVEAN

Benign

0.22

N;.;N;N;N;.;N;.;N;N

REVEL

Benign

0.050

Sift

Benign

0.62

T;.;T;T;T;.;T;.;T;T

Sift4G

Benign

0.55

T;T;T;T;T;T;T;T;T;T

Vest4

0.0

ClinPred

0.0046

GERP RS

4.2

gMVP

0.045

Mutation Taster

=99/1

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over