NM_004006.3(DMD):c.3276+1G>A AND Duchenne muscular dystrophy

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Aug 15, 2022
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:: RCV001854420.6

Allele description [Variation Report for NM_004006.3(DMD):c.3276+1G>A]

NM_004006.3(DMD):c.3276+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.3276+1G>A

HGVS:

NC_000023.11:g.32464585C>T
NG_012232.1:g.880025G>A
NM_000109.4:c.3252+1G>A
NM_004006.3:c.3276+1G>AMANE SELECT
NM_004009.3:c.3264+1G>A
NM_004010.3:c.2907+1G>A
LRG_199t1:c.3276+1G>A
LRG_199:g.880025G>A
NC_000023.10:g.32482702C>T
NM_004006.2:c.3276+1G>A

Links:

dbSNP: rs398123934

NCBI 1000 Genomes Browser:

rs398123934

Molecular consequence:

NM_000109.4:c.3252+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_004006.3:c.3276+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_004009.3:c.3264+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_004010.3:c.2907+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
SCV002290298	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Aug 15, 2022)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 27363342, 33644936, 16199547, 16770791, 25007885, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002290298

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Aug 15, 2022)

germline

clinical testing

PubMed (6)
[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

Citations

PubMed

Discovery of pathogenic variants in a large Korean cohort of inherited muscular disorders.

Park HJ, Jang H, Kim JH, Lee JH, Shin HY, Kim SM, Park KD, Yim SV, Lee JH, Choi YC.

Clin Genet. 2017 Mar;91(3):403-410. doi: 10.1111/cge.12826. Epub 2016 Jul 29.

PubMed [citation]

PMID:: 27363342

A single NGS-based assay covering the entire genomic sequence of the DMD gene facilitates diagnostic and newborn screening confirmatory testing.

Nallamilli BRR, Chaubey A, Valencia CA, Stansberry L, Behlmann AM, Ma Z, Mathur A, Shenoy S, Ganapathy V, Jagannathan L, Ramachander V, Ferlini A, Bean L, Hegde M.

Hum Mutat. 2021 May;42(5):626-638. doi: 10.1002/humu.24191. Epub 2021 Mar 19.

PubMed [citation]

PMID:: 33644936

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002290298.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 94583). Disruption of this splice site has been observed in individual(s) with clinical features of muscular dystrophy (PMID: 27363342, 33644936). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 24 of the DMD gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site 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).

#	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: Sep 29, 2024

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