Ehlers Danlos syndromes

Gene: SMAD2

Green List (high evidence)

SMAD2 (SMAD family member 2)
EnsemblGeneIds (GRCh38): ENSG00000175387
EnsemblGeneIds (GRCh37): ENSG00000175387
OMIM: 601366, Gene2Phenotype
SMAD2 is in 8 panels

5 reviews

Ivone Leong (Genomics England Curator)

Comment on phenotypes: Previous phenotypes:
Loeys-Dietz syndrome;LDS3;arterial aneurysms and dissections
Created: 18 Mar 2021, 2:05 p.m. | Last Modified: 18 Mar 2021, 2:05 p.m.
Panel Version: 2.44

Duncan Baker (Sheffield Genetics)

Green List (high evidence)

Eleanor Williams (Genomics England Curator)

I don't know

This gene was part of an initial gene list collated by Duncan Baker, Sheffield Diagnostic Genetics Service, January 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: SMAD2; Suggested initial gene rating: green
Created: 3 Apr 2019, 3:41 p.m.

Louise Daugherty (Genomics England Curator)

Green List (high evidence)

Comment on list classification: Changed from Red to Green as there is now enough evidence to support gene-disease association.
Note that the Red review for this gene is not a disagreement to the Green rating, but was added as a potential new gene for the EDS panel.
Created: 8 Aug 2018, 11:06 a.m.
After clinical review it was agreed there were sufficient cases for a gene:disease association. Other Loeys-Dietz syndrome genes are green on the EDS panel. The cases reported with SMAD2 have a connective tissue phenotype and there is also conceivable phenotypic overlap with kyphoscoliotic EDS, which further supports a green rating.
Created: 8 Aug 2018, 11:03 a.m.
PMID: 26247889 reports three unrelated cases with vascular disease, identified to have sequence variants in SMAD2.
Created: 30 Jul 2018, 3:54 p.m.
Past onto clinical team for further discussion to consider if this should be rated Green on the EDS panel, if so there are enough cases, it is already Green on the FTAAD panel. Loeys et al., (2018) GeneReview PMID: 20301312 notes only1%-5% of cases of with Loeys-Dietz Syndrome are attributed to Pathogenic Variants SMAD2. Two pathogenic variants in SMAD2 were initially reported in a series of 362 individuals with severe congenital heart disease Zaidi et al (2013) PMID: 23665959, the two individuals presented with dextrocardia associated with multiple other congenital heart defects. Subsequently, Micha D et al,. (2015) PMID: 26247889 reported three further unrelated cases with vascular disease, identified to have sequence variants in SMAD2, so if this disorder is relevant to EDS panel it could be made Green.
Created: 30 Jul 2018, 3:46 p.m.
included in EDS panel as Loeys-Dietz syndrome is a Heritable Connective Tissue Disorder.
Created: 30 Jul 2018, 3:45 p.m.

Anna de Burca (Genomics England Curator)

Red List (low evidence)

Rare cause of Loeys-Dietz syndrome, green on TAA panel; all other LDS genes are on this panel - should this be added here too?
Created: 30 Jul 2018, 12:45 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Loeys-Dietz syndrome

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • NHS GMS
  • Expert Review Green
Phenotypes
  • Loeys-Dietz syndrome, MONDO:0018954
OMIM
601366
Clinvar variants
Variants in SMAD2
Penetrance
None
Publications
Panels with this gene

History Filter Activity

18 Mar 2021, Gel status: 3

Set Phenotypes

Ivone Leong (Genomics England Curator)

Phenotypes for gene: SMAD2 were changed from Loeys-Dietz syndrome; LDS3; arterial aneurysms and dissections to Loeys-Dietz syndrome, MONDO:0018954

13 Mar 2019, Gel status: 3

Added New Source, Status Update

Eleanor Williams (Genomics England Curator)

Source NHS GMS was added to SMAD2. Rating Changed from Green List (high evidence) to Green List (high evidence)

8 Aug 2018, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: smad2 has been classified as Green List (High Evidence).

30 Jul 2018, Gel status: 1

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: SMAD2 were set to 26247899; 23665959; 20301312

30 Jul 2018, Gel status: 1

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: SMAD2 were set to 26247899; 23665959

30 Jul 2018, Gel status: 1

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: SMAD2 were set to 26247899; 23665959

30 Jul 2018, Gel status: 1

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: SMAD2 were set to Loeys-Dietz syndrome; LDS3; arterial aneurysms and dissections

30 Jul 2018, Gel status: 1

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: SMAD2 were set to 26247899

30 Jul 2018, Gel status: 1

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: SMAD2 were set to 26247899; 26247889

30 Jul 2018, Gel status: 1

Added New Source

Anna de Burca (Genomics England Curator)

SMAD2 was added to Ehlers-Danlos syndromes panel. Sources: Literature

30 Jul 2018, Gel status: 1

Created

Anna de Burca (Genomics England Curator)

SMAD2 was created by Anna de Burca