NM_004006.3(DMD):c.1603-2A>T AND Duchenne muscular dystrophy

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 5, 2020
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001384959.7

Allele description [Variation Report for NM_004006.3(DMD):c.1603-2A>T]

NM_004006.3(DMD):c.1603-2A>T

Gene:

DMD:dystrophin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xp21.1

Genomic location:

Preferred name:

NM_004006.3(DMD):c.1603-2A>T

HGVS:

NC_000023.11:g.32573848T>A
NG_012232.1:g.770762A>T
NM_000109.4:c.1579-2A>T
NM_004006.3:c.1603-2A>TMANE SELECT
NM_004009.3:c.1591-2A>T
NM_004010.3:c.1234-2A>T
LRG_199:g.770762A>T
NC_000023.10:g.32591965T>A

Links:

dbSNP: rs773779441

NCBI 1000 Genomes Browser:

rs773779441

Molecular consequence:

NM_000109.4:c.1579-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_004006.3:c.1603-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_004009.3:c.1591-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_004010.3:c.1234-2A>T - 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
SCV001584663	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 5, 2020)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 16199547, 16770791, 25007885, 16077730, 21851881, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001584663

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 5, 2020)

germline

clinical testing

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

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

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

Entries in the Leiden Duchenne muscular dystrophy mutation database: an overview of mutation types and paradoxical cases that confirm the reading-frame rule.

Aartsma-Rus A, Van Deutekom JC, Fokkema IF, Van Ommen GJ, Den Dunnen JT.

Muscle Nerve. 2006 Aug;34(2):135-44. Review.

PubMed [citation]

PMID:: 16770791

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001584663.4

#	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). Experimental studies have shown that disruption of this splice site affects mRNA splicing (PMID: 16077730). Disruption of this splice site has been observed in individual(s) with dystrophinopathy (PMID: 16077730, 21851881). This variant is also known as IVS13-2A>T. This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 13 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: Sep 29, 2024

ClinVar

Relating variation to medicine