NM_004006.3(DMD):c.3603+1G>A AND Duchenne muscular dystrophy

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Mar 15, 2024
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:: RCV000990683.13

Allele description [Variation Report for NM_004006.3(DMD):c.3603+1G>A]

NM_004006.3(DMD):c.3603+1G>A

Gene:

DMD:dystrophin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xp21.1

Genomic location:

Preferred name:

NM_004006.3(DMD):c.3603+1G>A

HGVS:

NC_000023.11:g.32454661C>T
NG_012232.1:g.889949G>A
NM_000109.4:c.3579+1G>A
NM_004006.3:c.3603+1G>AMANE SELECT
NM_004009.3:c.3591+1G>A
NM_004010.3:c.3234+1G>A
LRG_199:g.889949G>A
NC_000023.10:g.32472778C>T

Links:

dbSNP: rs1209389771

NCBI 1000 Genomes Browser:

rs1209389771

Molecular consequence:

NM_000109.4:c.3579+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_004006.3:c.3603+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_004009.3:c.3591+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_004010.3:c.3234+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

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
SCV001141706	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2017)	Pathogenic (Mar 15, 2024)	unknown	clinical testing	Citation Link,
SCV003247471	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 1, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 23536893, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001141706

Mendelics

criteria provided, single submitter

(Mendelics Assertion Criteria 2017)

Pathogenic
(Mar 15, 2024)

unknown

clinical testing

Citation Link,

SCV003247471

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 1, 2022)

germline

clinical testing

PubMed (2)
[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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Interplay between DMD point mutations and splicing signals in Dystrophinopathy phenotypes.

Juan-Mateu J, González-Quereda L, Rodríguez MJ, Verdura E, Lázaro K, Jou C, Nascimento A, Jiménez-Mallebrera C, Colomer J, Monges S, Lubieniecki F, Foncuberta ME, Pascual-Pascual SI, Molano J, Baiget M, Gallano P.

PLoS One. 2013;8(3):e59916. doi: 10.1371/journal.pone.0059916. Epub 2013 Mar 25.

PubMed [citation]

PMID:: 23536893
PMCID:: PMC3607557

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Mendelics, SCV001141706.2

#	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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003247471.2

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

Description

Disruption of this splice site has been observed in individual(s) with Duchenne muscular dystrophy (PMID: 23536893). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change affects a donor splice site in intron 26 of the DMD gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product. ClinVar contains an entry for this variant (Variation ID: 803890). For these reasons, this variant has been classified as Pathogenic. Studies have shown that disruption of this splice site results in activation of a cryptic splice site and introduces a premature termination codon (PMID: 23536893). The resulting mRNA is expected to undergo nonsense-mediated decay.

#	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: Nov 3, 2024

ClinVar

Relating variation to medicine