Limb girdle muscular dystrophy

Gene: DAG1

Green List (high evidence)

DAG1 (dystroglycan 1)
EnsemblGeneIds (GRCh38): ENSG00000173402
EnsemblGeneIds (GRCh37): ENSG00000173402
OMIM: 128239, Gene2Phenotype
DAG1 is in 14 panels

7 reviews

Ellen McDonagh (Genomics England Curator)

Comment on mode of inheritance: Confirmed in OMIM for relevant phenotype.
Created: 28 Nov 2019, 5:11 p.m. | Last Modified: 28 Nov 2019, 5:11 p.m.
Panel Version: 1.157
Comment on list classification: Promoted from Red to Green due to overall reviews and clinical comments from GLH representatives.
Created: 28 Nov 2019, 5:10 p.m. | Last Modified: 28 Nov 2019, 5:10 p.m.
Panel Version: 1.156

Chiara Marini Bettolo (NUTH)

Green List (high evidence)

Known form of LGMD2P or LGMDR16
Created: 21 Oct 2019, 1:27 p.m. | Last Modified: 21 Oct 2019, 1:27 p.m.
Panel Version: 1.97

Phenotypes
Limb-girdle muscular dystrophy

Publications

Louise Daugherty (Genomics England Curator)

I don't know

Review and rating from Natalie Forrester (SWGLH - Bristol Genetics) on behalf of South West GLH for GMS Neurology specialist test group.
Created: 30 Apr 2019, 11:45 a.m.

Natalie Forrester (SWGLH - Bristol Genetics)

I don't know

PubMed: 25503980 - 7-year-old Japanese boy with a very mild form of MDDGC9 presenting only as asymptomatic increased serum creatine kinase. Identified compound heterozygous missense mutations by WES. In vitro functional expression studies indicated that the mutations did not influence expression of dystroglycan, but did cause a defect in posttranslational modification. One variant is 0.013% (including 1 homoz) and other 0.2% (603 alleles including 1 homoz) in gnomAD - probably too common. PMID: 29036200 - some functional evidence for missense variants identified in paper above but considering MAF this should be used with caution. PubMed: 21388311 - mice with a homozygous T190M mutation in the Dag1 gene, which corresponds to the human T192M mutation, developed muscular dystrophy and neurologic motor impairment. Homoz vlimb-girdle muscular dystrophy-dystroglycanopathy and cognitive impairmentariant, absent from gnomAD and in patient with
Created: 30 Apr 2019, 11:24 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 9, 613818

Publications

Elizabeth Harris (Newcastle upon Tyne NHS Foundation Trust)

Note that an international expert review of the LGMD genes and nomenclature deemed that this is an LGMD causative gene (PMID: 30055862), I therefore strongly feel that this should be included in this panel list
Created: 29 Mar 2019, 1:11 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Limb girdle muscular dystrophy; congenital muscular dystrophy

Publications

Variants in this GENE are reported as part of current diagnostic practice

Sarah Leigh (Genomics England Curator)

Green List (high evidence)

Listed as associated with Limb Girdle Muscular Dystrophy by Gene Advisor (June 2016), Steve Abbs
Created: 27 Jul 2016, 8:21 a.m.
Comment on phenotypes: Also associated with Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 9, 616538
Created: 26 Jul 2016, 2:08 p.m.
Comment when marking as ready: Associated with phenotype in OMIM and G2P. Found in 2/4 sources. Expert reviewer recommends Amber. There are a total of three variants reported (could not find any more in the literature), one is found as a homozygote and the other two as compound heterozygotes in one patient. Functional studies done on the latter two variants.
Comment from Emma Clement: probably not sufficient evidence for green status (yet) although feel that very likely to be more LGMD mutations reported in this gene . Pains me to leave it orange as this is a really interesting gene. We searched for ages (research) for mutations in this gene, never found one, hopefully exome will turn up more.
appear to be rare.
Created: 9 Jun 2016, 12:39 p.m.
Comment on mode of inheritance: One patient reported as homozygous for one variant and another reported as a compound heterozygous for two additional variants
Created: 9 Jun 2016, 10:12 a.m.

Ellen Thomas (Genomics England Curator)

Comment on list classification: Definitely causes a more severe muscular dystrophy; evidence for LGMD phenotype less convincing.
Created: 29 May 2016, 3:31 p.m.

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Yorkshire and North East GLH
  • NHS GMS
  • South West GLH
  • Emory Genetics Laboratory
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 9, 613818
  • Limb girdle muscular dystrophy
  • congenital muscular dystrophy
  • Limb-girdle muscular dystrophy
OMIM
128239
Clinvar variants
Variants in DAG1
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

28 Nov 2019, Gel status: 3

Entity classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

Gene: dag1 has been classified as Green List (High Evidence).

28 Nov 2019, Gel status: 3

Set mode of inheritance

Ellen McDonagh (Genomics England Curator)

Mode of inheritance for gene: DAG1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal

28 Nov 2019, Gel status: 3

Entity classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

Gene: dag1 has been classified as Green List (High Evidence).

13 May 2019, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

Source Yorkshire and North East GLH was added to DAG1.

13 May 2019, Gel status: 1

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: DAG1 were changed from Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 9, 613818; Limb girdle muscular dystrophy; congenital muscular dystrophy to Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 9, 613818; Limb girdle muscular dystrophy; congenital muscular dystrophy; Limb-girdle muscular dystrophy

13 May 2019, Gel status: 1

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: DAG1 were set to 21388311; 25503980; 25503980; 29036200; 21388311; 14678799

30 Apr 2019, Gel status: 1

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: DAG1 were changed from Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 9, 613818 to Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 9, 613818; Limb girdle muscular dystrophy; congenital muscular dystrophy

30 Apr 2019, Gel status: 1

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: DAG1 were set to 21388311; 25503980; 25503980; 29036200; 21388311; 14678799

30 Apr 2019, Gel status: 1

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: DAG1 were set to 21388311; 25503980

30 Apr 2019, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to DAG1.

30 Apr 2019, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

Source South West GLH was added to DAG1.

27 Jul 2016, Gel status: 1

panel promoted to version 1

Sarah Leigh (Genomics England Curator)

Comments from Fiona Karet included. A Green review for each gene relevant for this panel on the Gene Advisor download has been included.

26 Jul 2016, Gel status: 1

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for DAG1 were set to Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 9, 613818

26 Jul 2016, Gel status: 1

Gene classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

This gene has been classified as Red List (Low Evidence).

9 Jun 2016, Gel status: 2

Gene classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

This gene has been classified as Amber List (Moderate Evidence).

9 Jun 2016, Gel status: 2

Gene classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

This gene has been classified as Amber List (Moderate Evidence).

9 Jun 2016, Gel status: 4

Gene classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

9 Jun 2016, Gel status: 2

Set Mode of Inheritance

Sarah Leigh (Genomics England Curator)

Mode of inheritance for DAG1 was changed to BIALLELIC, autosomal or pseudoautosomal

9 Jun 2016, Gel status: 2

Set publications

Sarah Leigh (Genomics England Curator)

Publications for DAG1 were set to 21388311; 25503980

9 Jun 2016, Gel status: 2

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for DAG1 were set to Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 9, 613818; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 9, 616538

29 May 2016, Gel status: 2

Gene classified by Genomics England curator

Ellen Thomas (Genomics England Curator)

This gene has been classified as Amber List (Moderate Evidence).

28 Jul 2015, Gel status: 2

Added New Source

Ellen McDonagh (Genomics England Curator)

DAG1 was added to Limb girdle muscular dystrophypanel. Sources: Radboud University Medical Center, Nijmegen,Emory Genetics Laboratory

28 Jul 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

DAG1 was added to Limb girdle muscular dystrophypanel. Sources: Radboud University Medical Center, Nijmegen,Emory Genetics Laboratory