NM_004006.3(DMD):c.2804-2A>C AND Duchenne muscular dystrophy

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jan 14, 2021
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:: RCV000201191.8

Allele description [Variation Report for NM_004006.3(DMD):c.2804-2A>C]

NM_004006.3(DMD):c.2804-2A>C

Gene:

DMD:dystrophin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xp21.1

Genomic location:

Preferred name:

NM_004006.3(DMD):c.2804-2A>C

HGVS:

NC_000023.11:g.32472311T>G
NG_012232.1:g.872299A>C
NM_000109.4:c.2780-2A>C
NM_004006.3:c.2804-2A>CMANE SELECT
NM_004009.3:c.2792-2A>C
NM_004010.3:c.2435-2A>C
LRG_199t1:c.2804-2A>C
LRG_199:g.872299A>C
NC_000023.10:g.32490428T>G
NM_004006.2:c.2804-2A>C

Links:

dbSNP: rs794727357

NCBI 1000 Genomes Browser:

rs794727357

Molecular consequence:

NM_000109.4:c.2780-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_004006.3:c.2804-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_004009.3:c.2792-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_004010.3:c.2435-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000255716	Athena Diagnostics Inc	criteria provided, single submitter (Athena Diagnostics Criteria)	Pathogenic (Oct 21, 2013)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 15351422, 26467025
SCV001215811	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 14, 2021)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 16199547, 16770791, 25007885, 15351422, 27593222, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000255716

Athena Diagnostics Inc

criteria provided, single submitter

(Athena Diagnostics Criteria)

Pathogenic
(Oct 21, 2013)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV001215811

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 14, 2021)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

Description

X-linked recessive inheritance: SCV000255716

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

Citations

PubMed

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]

PMID:: 26467025
PMCID:: PMC4737317

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

See all PubMed Citations (7)

Details of each submission

From Athena Diagnostics Inc, SCV000255716.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

#	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 Invitae, SCV001215811.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

For these reasons, this variant has been classified as Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in DMD are known to be pathogenic (PMID: 16770791, 25007885). This variant has been observed to be hemizygous in individuals affected with Duchenne or Becker muscular dystrophy (PMID: 15351422, 27593222). ClinVar contains an entry for this variant (Variation ID: 217190). This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 21 of the DMD gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product.

#	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

Last Updated: Mar 16, 2024

ClinVar

Relating variation to medicine