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NM_004006.3(DMD):c.10223+1G>A AND Qualitative or quantitative defects of dystrophin

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jul 26, 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:
RCV003323388.2

Allele description [Variation Report for NM_004006.3(DMD):c.10223+1G>A]

NM_004006.3(DMD):c.10223+1G>A

Gene:
DMD:dystrophin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xp21.2
Genomic location:
Preferred name:
NM_004006.3(DMD):c.10223+1G>A
HGVS:
  • NC_000023.11:g.31178668C>T
  • NG_012232.1:g.2165942G>A
  • NM_000109.4:c.10199+1G>A
  • NM_004006.3:c.10223+1G>AMANE SELECT
  • NM_004009.3:c.10211+1G>A
  • NM_004010.3:c.9854+1G>A
  • NM_004011.4:c.6200+1G>A
  • NM_004012.4:c.6191+1G>A
  • NM_004013.3:c.2843+1G>A
  • NM_004014.3:c.2036+1G>A
  • NM_004015.3:c.1019+1G>A
  • NM_004016.3:c.1019+1G>A
  • NM_004017.3:c.1019+1G>A
  • NM_004018.3:c.1019+1G>A
  • NM_004019.3:c.1020G>A
  • NM_004020.4:c.2843+1G>A
  • NM_004021.3:c.2843+1G>A
  • NM_004022.3:c.2843+1G>A
  • NM_004023.3:c.2843+1G>A
  • NP_004010.1:p.Thr340=
  • LRG_199t1:c.10223+1G>A
  • LRG_199:g.2165942G>A
  • NC_000023.10:g.31196785C>T
  • NM_004006.2:c.10223+1G>A
Nucleotide change:
IVS70, G-A, +1
Links:
OMIM: 300377.0068; dbSNP: rs398123834
NCBI 1000 Genomes Browser:
rs398123834
Molecular consequence:
  • NM_000109.4:c.10199+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_004006.3:c.10223+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_004009.3:c.10211+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_004010.3:c.9854+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_004011.4:c.6200+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_004012.4:c.6191+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_004013.3:c.2843+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_004014.3:c.2036+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_004015.3:c.1019+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_004016.3:c.1019+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_004017.3:c.1019+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_004018.3:c.1019+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_004020.4:c.2843+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_004021.3:c.2843+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_004022.3:c.2843+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_004023.3:c.2843+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_004019.3:c.1020G>A - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004029847Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Pathogenic
(Jul 26, 2023) 		germlineclinical testing

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

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Mutational spectrum of DMD mutations in dystrophinopathy patients: application of modern diagnostic techniques to a large cohort.

Flanigan KM, Dunn DM, von Niederhausern A, Soltanzadeh P, Gappmaier E, Howard MT, Sampson JB, Mendell JR, Wall C, King WM, Pestronk A, Florence JM, Connolly AM, Mathews KD, Stephan CM, Laubenthal KS, Wong BL, Morehart PJ, Meyer A, Finkel RS, Bonnemann CG, Medne L, et al.

Hum Mutat. 2009 Dec;30(12):1657-66. doi: 10.1002/humu.21114.

PubMed [citation]
PMID:
19937601
PMCID:
PMC3404892

Analysis of Dp71 contribution in the severity of mental retardation through comparison of Duchenne and Becker patients differing by mutation consequences on Dp71 expression.

Daoud F, Angeard N, Demerre B, Martie I, Benyaou R, Leturcq F, Cossée M, Deburgrave N, Saillour Y, Tuffery S, Urtizberea A, Toutain A, Echenne B, Frischman M, Mayer M, Desguerre I, Estournet B, Réveillère C, Penisson-Besnier, Cuisset JM, Kaplan JC, Héron D, et al.

Hum Mol Genet. 2009 Oct 15;18(20):3779-94. doi: 10.1093/hmg/ddp320. Epub 2009 Jul 14.

PubMed [citation]
PMID:
19602481
See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004029847.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

Variant summary: DMD c.10223+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: Four predict the variant abolishes a 5' splicing donor site. At least one publication reported that this variant affects mRNA splicing, causing out-of-frame exon 70 skipping, as demonstrated in patient derived mRNA samples (Daoud_2009). The variant was absent in 181746 control chromosomes (gnomAD). c.10223+1G>A has been reported in the literature in several individuals affected with Dystrophinopathies (e.g. Flanigan_2009, Daoud_2009, Neri_2020). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 19937601, 19602481, 32194622). Five submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 10, 2024