rs1800275

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004006.3(DMD):c.7096A>C(p.Lys2366Gln) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 1,200,242 control chromosomes in the GnomAD database, including 21,883 homozygotes. There are 83,031 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.21 ( 1952 hom., 6801 hem., cov: 23)

Exomes 𝑓: 0.22 ( 19931 hom. 76230 hem. )

Consequence

DMD
NM_004006.3 missense, splice_region

Scores

Splicing: ADA: 0.06784

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 2.61

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0033306181).

BP6

Variant X-31875190-T-G is Benign according to our data. Variant chrX-31875190-T-G is described in ClinVar as [Benign]. Clinvar id is 166706.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-31875190-T-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMD	NM_004006.3 link	c.7096A>C	p.Lys2366Gln	missense_variant, splice_region_variant	Exon 48 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.7096A>C	p.Lys2366Gln	missense_variant, splice_region_variant	Exon 48 of 79	1	NM_004006.3	ENSP00000354923.3		A0A075B6G3

Frequencies

GnomAD3 genomes

AF:

0.210

AC:

23299

AN:

111060

Hom.:

1954

Cov.:

AF XY:

0.204

AC XY:

6794

AN XY:

33302

show subpopulations

Gnomad AFR

AF:

0.168

Gnomad AMI

AF:

0.321

Gnomad AMR

AF:

0.384

Gnomad ASJ

AF:

0.184

Gnomad EAS

AF:

0.102

Gnomad SAS

AF:

0.128

Gnomad FIN

AF:

0.189

Gnomad MID

AF:

0.224

Gnomad NFE

AF:

0.213

Gnomad OTH

AF:

0.221

GnomAD3 exomes

AF:

0.234

AC:

39146

AN:

167586

Hom.:

4643

AF XY:

0.199

AC XY:

10823

AN XY:

54274

show subpopulations

Gnomad AFR exome

AF:

0.171

Gnomad AMR exome

AF:

0.516

Gnomad ASJ exome

AF:

0.189

Gnomad EAS exome

AF:

0.0987

Gnomad SAS exome

AF:

0.138

Gnomad FIN exome

AF:

0.192

Gnomad NFE exome

AF:

0.208

Gnomad OTH exome

AF:

0.206

GnomAD4 exome

AF:

0.219

AC:

238860

AN:

1089132

Hom.:

19931

Cov.:

AF XY:

0.214

AC XY:

76230

AN XY:

356672

show subpopulations

Gnomad4 AFR exome

AF:

0.171

Gnomad4 AMR exome

AF:

0.506

Gnomad4 ASJ exome

AF:

0.195

Gnomad4 EAS exome

AF:

0.0868

Gnomad4 SAS exome

AF:

0.151

Gnomad4 FIN exome

AF:

0.197

Gnomad4 NFE exome

AF:

0.221

Gnomad4 OTH exome

AF:

0.206

GnomAD4 genome

AF:

0.210

AC:

23297

AN:

111110

Hom.:

1952

Cov.:

AF XY:

0.204

AC XY:

6801

AN XY:

33362

show subpopulations

Gnomad4 AFR

AF:

0.169

Gnomad4 AMR

AF:

0.384

Gnomad4 ASJ

AF:

0.184

Gnomad4 EAS

AF:

0.102

Gnomad4 SAS

AF:

0.128

Gnomad4 FIN

AF:

0.189

Gnomad4 NFE

AF:

0.213

Gnomad4 OTH

AF:

0.217

Alfa

AF:

0.211

Hom.:

13710

Bravo

AF:

0.231

TwinsUK

AF:

0.228

AC:

844

ALSPAC

AF:

0.217

AC:

626

ESP6500AA

AF:

0.182

AC:

696

ESP6500EA

AF:

0.218

AC:

1465

ExAC

AF:

0.220

AC:

26648

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Duchenne muscular dystrophy

Benign:3

May 28, 2019

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

- -

not specified

Benign:2

Feb 20, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

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 RefSeq base and residue are not consistent across bu ilds. The variant (c.7096C) represents the Alamut RefSeq base and minor allele. This allele (C) has been identified in 22% (1465/6727) of European American chro mosomes and 18% (696/3833) of African American chromosomes by the NHLBI Exome Se quencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs1800275) and thus m eets criteria to be classified as benign. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 21, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

0.13

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

.;.;T;.;.

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.65

T;T;.;T;T

MetaRNN

Benign

0.0033

T;T;T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.40

N;.;N;.;N

REVEL

Benign

0.092

Sift

Benign

0.20

T;.;T;.;T

Sift4G

Benign

0.51

T;T;T;T;T

Polyphen

1.0

.;.;D;.;.

Vest4

0.54, 0.25, 0.55, 0.25

MPC

0.016

ClinPred

0.017

GERP RS

5.2

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.068

dbscSNV1_RF

Benign

0.50

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