NM_004006.3(DMD):c.5026-2A>G AND Duchenne muscular dystrophy

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: May 28, 2019
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:: RCV000691896.8

Allele description [Variation Report for NM_004006.3(DMD):c.5026-2A>G]

NM_004006.3(DMD):c.5026-2A>G

Gene:

DMD:dystrophin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xp21.1

Genomic location:

Preferred name:

NM_004006.3(DMD):c.5026-2A>G

HGVS:

NC_000023.11:g.32364712T>C
NG_012232.1:g.979898A>G
NM_000109.4:c.5002-2A>G
NM_004006.3:c.5026-2A>GMANE SELECT
NM_004009.3:c.5014-2A>G
NM_004010.3:c.4657-2A>G
NM_004011.4:c.1003-2A>G
NM_004012.4:c.994-2A>G
LRG_199t1:c.5026-2A>G
LRG_199:g.979898A>G
NC_000023.10:g.32382829T>C
NM_004006.2:c.5026-2A>G

Links:

dbSNP: rs1569559849

NCBI 1000 Genomes Browser:

rs1569559849

Molecular consequence:

NM_000109.4:c.5002-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_004006.3:c.5026-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_004009.3:c.5014-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_004010.3:c.4657-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_004011.4:c.1003-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_004012.4:c.994-2A>G - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000819695	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Dec 21, 2018)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16199547, 16770791, 25007885, 28492532
SCV001141670	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2017)	Pathogenic (May 28, 2019)	unknown	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000819695

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Dec 21, 2018)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV001141670

Mendelics

criteria provided, single submitter

(Mendelics Assertion Criteria 2017)

Pathogenic
(May 28, 2019)

unknown

clinical testing

Citation Link

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	unknown	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 (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000819695.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change affects an acceptor splice site in intron 35 of the DMD gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely 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). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with DMD-related disease. ClinVar contains an entry for this variant (Variation ID: 570910). This variant is not present in population databases (ExAC no frequency).

#	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 Mendelics, SCV001141670.1

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

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

Last Updated: Nov 10, 2024

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