NM_004006.3(DMD):c.1812+1G>A AND Qualitative or quantitative defects of dystrophin

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 27, 2023
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:: RCV003155089.2

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:: Qualitative or quantitative defects of dystrophin
Identifiers:: MONDO: MONDO:0016147; MedGen: C5679787

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003844269	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Feb 27, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 17259292, 32194622, 31404137 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003844269

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Feb 27, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

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

Citations

PubMed

Measurement of the clinical utility of a combined mutation detection protocol in carriers of Duchenne and Becker muscular dystrophy.

Taylor PJ, Maroulis S, Mullan GL, Pedersen RL, Baumli A, Elakis G, Piras S, Walsh C, Prósper-Gutiérrez B, De La Puente-Alonso F, Bell CG, Mowat DR, Johnston HM, Buckley MF.

J Med Genet. 2007 Jun;44(6):368-72. Epub 2007 Jan 26.

PubMed [citation]

PMID:: 17259292
PMCID:: PMC2740880

The Genetic Landscape of Dystrophin Mutations in Italy: A Nationwide Study.

Neri M, Rossi R, Trabanelli C, Mauro A, Selvatici R, Falzarano MS, Spedicato N, Margutti A, Rimessi P, Fortunato F, Fabris M, Gualandi F, Comi G, Tedeschi S, Seia M, Fiorillo C, Traverso M, Bruno C, Giardina E, Piemontese MR, Merla G, Cau M, et al.

Front Genet. 2020;11:131. doi: 10.3389/fgene.2020.00131.

PubMed [citation]

PMID:: 32194622
PMCID:: PMC7063120

See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV003844269.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

Variant summary: DMD c.1812+1G>A is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: One predict the variant abolishes the canonical 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 1.6e-05 in 182866 control chromosomes (gnomAD). c.1812+1G>A has been reported in the literature in individuals affected with Dystrophinopathies (example: Taylor_2007, Neri_2017, Wang_2019). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Ten clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was 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

Last Updated: May 12, 2024

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