NM_004006.3(DMD):c.1812+1G>A AND Duchenne muscular dystrophy

Germline classification:: Pathogenic (4 submissions)
Last evaluated:: Dec 22, 2023
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:: RCV000201160.13

Allele description [Variation Report for NM_004006.3(DMD):c.1812+1G>A]

NM_004006.3(DMD):c.1812+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.1812+1G>A

HGVS:

NC_000023.11:g.32573529C>T
NG_012232.1:g.771081G>A
NM_000109.4:c.1788+1G>A
NM_004006.3:c.1812+1G>AMANE SELECT
NM_004009.3:c.1800+1G>A
NM_004010.3:c.1443+1G>A
LRG_199t1:c.1812+1G>A
LRG_199:g.771081G>A
NC_000023.10:g.32591646C>T
NM_004006.2:c.1812+1G>A

Links:

dbSNP: rs373286166

NCBI 1000 Genomes Browser:

rs373286166

Molecular consequence:

NM_000109.4:c.1788+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_004006.3:c.1812+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_004009.3:c.1800+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_004010.3:c.1443+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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000692204	Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 7, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001132171	Counsyl	no assertion criteria provided	Likely pathogenic (Dec 7, 2018)	unknown	clinical testing	PubMed (5) [See all records that cite these PMIDs] 19937601, 22223181, 17854090, 17259292, 27930565
SCV001205869	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 22, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 17259292, 19937601, 32194622, 27930565, 28492532
SCV002761495	Genetics and Molecular Pathology, SA Pathology See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 14, 2021)	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	yes	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
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Rapid, comprehensive analysis of the dystrophin transcript by a custom micro-fluidic exome array.

Bovolenta M, Scotton C, Falzarano MS, Gualandi F, Ferlini A.

Hum Mutat. 2012 Mar;33(3):572-81. doi: 10.1002/humu.22017. Epub 2012 Jan 25.

PubMed [citation]

PMID:: 22223181

Array-MLPA: comprehensive detection of deletions and duplications and its application to DMD patients.

Zeng F, Ren ZR, Huang SZ, Kalf M, Mommersteeg M, Smit M, White S, Jin CL, Xu M, Zhou DW, Yan JB, Chen MJ, van Beuningen R, Huang SZ, den Dunnen J, Zeng YT, Wu Y.

Hum Mutat. 2008 Jan;29(1):190-7.

PubMed [citation]

PMID:: 17854090

See all PubMed Citations (8)

Details of each submission

From Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital, SCV000692204.1

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

#	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

From Counsyl, SCV001132171.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

#	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 Invitae, SCV001205869.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change affects a donor splice site in intron 15 of the DMD gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened protein product. This variant is present in population databases (rs373286166, gnomAD 0.005%). Disruption of this splice site has been observed in individuals with Becker or Duchenne muscular dystrophy (PMID: 17259292, 19937601, 27930565, 32194622). ClinVar contains an entry for this variant (Variation ID: 162497). Studies have shown that disruption of this splice site results in skipping of exon 15, but is expected to preserve the integrity of the reading-frame (PMID: 27930565). 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	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Genetics and Molecular Pathology, SA Pathology, SCV002761495.1

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

#	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: May 12, 2024

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