rs1800280

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

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. 12/17 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:11

Conservation

PhyloP100: 0.643

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 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 id is 166667.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-31478233-C-T is described in Lovd as [Benign].

BS2

High Homozygotes in GnomAd at 34555 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DMD	NM_004006.3 linkuse as main transcript	c.8810G>A	p.Arg2937Gln	missense_variant	59/79	ENST00000357033.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DMD	ENST00000357033.9 linkuse as main transcript	c.8810G>A	p.Arg2937Gln	missense_variant	59/79	1	NM_004006.3	P4

Frequencies

GnomAD3 genomes

AF:

0.939

AC:

102725

AN:

109406

Hom.:

34555

Cov.:

AF XY:

0.933

AC XY:

29509

AN XY:

31616

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

GnomAD3 exomes

AF:

0.898

AC:

164218

AN:

182910

Hom.:

47505

AF XY:

0.890

AC XY:

59954

AN XY:

67392

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 SAS exome

AF:

0.706

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

Gnomad4 AFR exome

AF:

0.990

Gnomad4 AMR exome

AF:

0.803

Gnomad4 ASJ exome

AF:

0.979

Gnomad4 EAS exome

AF:

0.939

Gnomad4 SAS exome

AF:

0.715

Gnomad4 FIN exome

AF:

0.940

Gnomad4 NFE exome

AF:

0.935

Gnomad4 OTH exome

AF:

0.922

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

Gnomad4 AFR

AF:

0.986

Gnomad4 AMR

AF:

0.858

Gnomad4 ASJ

AF:

0.977

Gnomad4 EAS

AF:

0.929

Gnomad4 SAS

AF:

0.682

Gnomad4 FIN

AF:

0.944

Gnomad4 NFE

AF:

0.938

Gnomad4 OTH

AF:

0.938

Alfa

AF:

0.933

Hom.:

82819

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:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 26, 2014	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. -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 02, 2016	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Duchenne muscular dystrophy

Benign:3

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -

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

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Apr 20, 2017

- -

Dilated cardiomyopathy 3B

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Nov 29, 2023

- -

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

Dann

Benign

0.83

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

MutationTaster

Benign

1.0

P;P;P;P;P;P;P

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

Polyphen

0.0

.;.;B;B;B;.;B;.;.;B

Vest4

0.056, 0.068, 0.058, 0.071, 0.041, 0.040, 0.077

MPC

0.016

ClinPred

0.0046

GERP RS

4.2

gMVP

0.045

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over