rs372600090

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP6BS2

The NM_004006.3(DMD):c.8212T>C(p.Trp2738Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,209,545 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., 6 hem., cov: 23)

Exomes 𝑓: 0.0000082 ( 0 hom. 0 hem. )

Consequence

DMD
NM_004006.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: 9.10

Publications

0 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: Likely_benign. The variant received -5 ACMG points.

BP6

Variant X-31627678-A-G is Benign according to our data. Variant chrX-31627678-A-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 264464. Variant chrX-31627678-A-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 264464. Variant chrX-31627678-A-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 264464. Variant chrX-31627678-A-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 264464. Variant chrX-31627678-A-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 264464. Variant chrX-31627678-A-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 264464. Variant chrX-31627678-A-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 264464. Variant chrX-31627678-A-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 264464. Variant chrX-31627678-A-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 264464. Variant chrX-31627678-A-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 264464. Variant chrX-31627678-A-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 264464. Variant chrX-31627678-A-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 264464. Variant chrX-31627678-A-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 264464. Variant chrX-31627678-A-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 264464. Variant chrX-31627678-A-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 264464. Variant chrX-31627678-A-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 264464. Variant chrX-31627678-A-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 264464. Variant chrX-31627678-A-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 264464. Variant chrX-31627678-A-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 264464. Variant chrX-31627678-A-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 264464. Variant chrX-31627678-A-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 264464. Variant chrX-31627678-A-G is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 264464.

BS2

High AC in GnomAd4 at 15 XL,AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMD	NM_004006.3 link	c.8212T>C	p.Trp2738Arg	missense_variant	Exon 55 of 79	ENST00000357033.9	NP_003997.2	P11532

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMD	ENST00000357033.9 link	c.8212T>C	p.Trp2738Arg	missense_variant	Exon 55 of 79	1	NM_004006.3	ENSP00000354923.3		A0A075B6G3

Frequencies

GnomAD3 genomes

AF:

0.000134

AC:

AN:

112196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000485

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000276

AC:

AN:

181388

AF XY:

0.0000150

show subpopulations

Gnomad AFR exome

AF:

0.000383

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000820

AC:

AN:

1097349

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

362877

show subpopulations

African (AFR)

AF:

0.000303

AC:

AN:

26389

American (AMR)

AF:

0.00

AC:

AN:

35202

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19374

East Asian (EAS)

AF:

0.00

AC:

AN:

30168

South Asian (SAS)

AF:

0.00

AC:

AN:

54087

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40405

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3964

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

841712

Other (OTH)

AF:

0.0000217

AC:

AN:

46048

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.436

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:

0.000134

AC:

AN:

112196

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

34360

show subpopulations

African (AFR)

AF:

0.000485

AC:

AN:

30913

American (AMR)

AF:

0.00

AC:

AN:

10513

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2641

East Asian (EAS)

AF:

0.00

AC:

AN:

3598

South Asian (SAS)

AF:

0.00

AC:

AN:

2711

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6059

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53321

Other (OTH)

AF:

0.00

AC:

AN:

1514

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000189

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1

May 30, 2019

Revvity Omics, Revvity

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Dec 06, 2017

GeneDx

Significance:Likely 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. -

Duchenne muscular dystrophy

Benign:1

Oct 24, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cardiovascular phenotype

Benign:1

Apr 07, 2025

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Pathogenic

0.23

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

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

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.89

D;.;.;.;D;.;D;D;.

M_CAP

Pathogenic

0.48

MetaRNN

Uncertain

0.48

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

MetaSVM

Benign

-0.70

PhyloP100

9.1

PrimateAI

Pathogenic

0.80

PROVEAN

Uncertain

-2.9

D;N;D;N;.;D;.;D;N

REVEL

Uncertain

0.47

Sift

Benign

0.047

D;T;T;T;.;D;.;D;T

Sift4G

Benign

0.13

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

Polyphen

0.72, 1.0, 0.64

.;P;D;P;.;D;.;.;P

Vest4

0.87, 0.89, 0.87, 0.83, 0.88, 0.83, 0.85, 0.87

MutPred

0.58

.;.;.;.;.;.;.;Gain of disorder (P = 0.0016);.;

MVP

0.86

MPC

0.088

ClinPred

0.45

GERP RS

5.8

gMVP

0.74

Mutation Taster

=98/2

polymorphism

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over