NM_004006.3(DMD):c.8038C>T (p.Arg2680Ter) AND Duchenne muscular dystrophy

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Aug 10, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000201174.13

Allele description [Variation Report for NM_004006.3(DMD):c.8038C>T (p.Arg2680Ter)]

NM_004006.3(DMD):c.8038C>T (p.Arg2680Ter)

Gene:

DMD:dystrophin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xp21.1

Genomic location:

Preferred name:

NM_004006.3(DMD):c.8038C>T (p.Arg2680Ter)

HGVS:

NC_000023.11:g.31627852G>A
NG_012232.1:g.1716758C>T
NM_000109.4:c.8014C>T
NM_004006.3:c.8038C>TMANE SELECT
NM_004009.3:c.8026C>T
NM_004010.3:c.7669C>T
NM_004011.4:c.4015C>T
NM_004012.4:c.4006C>T
NM_004013.3:c.658C>T
NM_004020.4:c.658C>T
NM_004021.3:c.658C>T
NM_004022.3:c.658C>T
NM_004023.3:c.658C>T
NP_000100.3:p.Arg2672Ter
NP_003997.1:p.Arg2680Ter
NP_003997.2:p.Arg2680Ter
NP_004000.1:p.Arg2676Ter
NP_004001.1:p.Arg2557Ter
NP_004002.3:p.Arg1339Ter
NP_004003.2:p.Arg1336Ter
NP_004004.2:p.Arg220Ter
NP_004011.3:p.Arg220Ter
NP_004012.2:p.Arg220Ter
NP_004013.2:p.Arg220Ter
NP_004014.2:p.Arg220Ter
LRG_199t1:c.8038C>T
LRG_199:g.1716758C>T
LRG_199p1:p.Arg2680Ter
NC_000023.10:g.31645969G>A
NM_004006.2:c.8038C>T

Protein change:

R1336*

Links:

dbSNP: rs863225011

NCBI 1000 Genomes Browser:

rs863225011

Molecular consequence:

NM_000109.4:c.8014C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_004006.3:c.8038C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_004009.3:c.8026C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_004010.3:c.7669C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_004011.4:c.4015C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_004012.4:c.4006C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_004013.3:c.658C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_004020.4:c.658C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_004021.3:c.658C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_004022.3:c.658C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_004023.3:c.658C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Duchenne muscular dystrophy (DMD)
Synonyms:: Muscular dystrophy, pseudohypertrophic progressive, Duchenne type
Identifiers:: MONDO: MONDO:0010679; MedGen: C0013264; Orphanet: 98896; OMIM: 310200

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000550331	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 10, 2022)	germline	clinical testing	PubMed (11) [See all records that cite these PMIDs] 15351422, 17041906, 18583217, 19835634, 19937601, 21396098, 25612904, 25636106, 16770791, 25007885, 28492532
SCV004048201	Neuberg Centre For Genomic Medicine, NCGM	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000550331

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 10, 2022)

germline

clinical testing

PubMed (11)
[See all records that cite these PMIDs]

SCV004048201

Neuberg Centre For Genomic Medicine, NCGM

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

The role of muscle biopsy in analysis of the dystrophin gene in Duchenne muscular dystrophy: experience of a national referral centre.

Tuffery-Giraud S, Saquet C, Chambert S, Echenne B, Marie Cuisset J, Rivier F, Cossée M, Philippe C, Monnier N, Bieth E, Recan D, Antoinette Voelckel M, Perelman S, Lambert JC, Malcolm S, Claustres M.

Neuromuscul Disord. 2004 Oct;14(10):650-8.

PubMed [citation]

PMID:: 15351422

Protein- and mRNA-based phenotype-genotype correlations in DMD/BMD with point mutations and molecular basis for BMD with nonsense and frameshift mutations in the DMD gene.

Deburgrave N, Daoud F, Llense S, Barbot JC, Récan D, Peccate C, Burghes AH, Béroud C, Garcia L, Kaplan JC, Chelly J, Leturcq F.

Hum Mutat. 2007 Feb;28(2):183-95.

PubMed [citation]

PMID:: 17041906

See all PubMed Citations (12)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000550331.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (11)

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 217213). This premature translational stop signal has been observed in individuals with Duchenne muscular dystrophy (DMD) (PMID: 15351422, 16770791, 17041906, 18583217, 19835634, 19937601, 21396098, 25612904, 25636106). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg2680*) in the DMD gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DMD are known to be pathogenic (PMID: 16770791, 25007885).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Neuberg Centre For Genomic Medicine, NCGM, SCV004048201.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This sequence change creates a premature translational stop signal at codon 2680 (p.Arg2680*) of the DMD gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DMD are known to be pathogenic (Aartsma‐Rus et al). This variant has been reported in individuals affected with Duchenne muscular dystrophy (DMD) (Magri, Francesca, et al,Tuffery-Giraud, Sylvie, et al). This variant has been reported to the ClinVar database as Pathogenic. The nucleotide change in DMD is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. For these reasons, this variant has been classified as pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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