Ehlers Danlos syndromes

Gene: SMAD3

Green List (high evidence)

SMAD3 (SMAD family member 3)
EnsemblGeneIds (GRCh38): ENSG00000166949
EnsemblGeneIds (GRCh37): ENSG00000166949
OMIM: 603109, Gene2Phenotype
SMAD3 is in 16 panels

5 reviews

Duncan Baker (Sheffield Genetics)

Green List (high evidence)

Eleanor Williams (Genomics England Curator)

I don't know

Note one case with a biallelic variant reported:
PMID: 32935439 - Baskin et al 2020 - first report of a LDS patient with biallelic SMAD3 variants (affecting splice site). Proband had classic Loeys-Dietz features, including dysmorphic facial features, significant scoliosis, and pectus excavatum, arachnodactyly, severe aortic root dilation, and diffuse arterial tortuosity. His parents are each heterozygous for the likely pathogenic variant and are more mildly affected.
Created: 28 Jul 2021, 12:25 a.m. | Last Modified: 28 Jul 2021, 12:25 a.m.
Panel Version: 2.60
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: SMAD3; Suggested initial gene rating: green
Created: 3 Apr 2019, 3:41 p.m.

Angela Brady (Nhs)

Green List (high evidence)

Neeti Ghali (NWTRGS, Northwick Park Hospital)

Green List (high evidence)

Louise Daugherty (Genomics England Curator)

I don't know

Refer to clinical team for further discussion on wether we should include this gene on the EDS panel. There is clinical overlap between EDS and other Heritable Connective Tissue Disorders.
Created: 28 Apr 2017, 11:50 a.m.
Comment on phenotypes: included in EDS panel as Loeys-Dietz syndrome is a Heritable Connective Tissue Disorder.
Created: 26 Apr 2017, 1:32 p.m.
Comment on list classification: Green due to enough evidence in the literature
Created: 26 Apr 2017, 11:50 a.m.
Comment on publications: Added publications to support gene is involved in the disorder(s) in 3 or more unrelated cases
Created: 26 Apr 2017, 11:50 a.m.

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • NHS GMS
  • Illumina TruGenome Clinical Sequencing Services
  • Expert Review Green
  • Expert list
  • Emory Genetics Laboratory
Phenotypes
  • Loeys-Dietz syndrome 3, OMIM:613795
OMIM
603109
Clinvar variants
Variants in SMAD3
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

18 Mar 2021, Gel status: 3

Set Phenotypes

Ivone Leong (Genomics England Curator)

Phenotypes for gene: SMAD3 were changed from Loeys-Dietz syndrome 3, 613795 to Loeys-Dietz syndrome 3, OMIM:613795

13 Mar 2019, Gel status: 3

Added New Source, Status Update

Eleanor Williams (Genomics England Curator)

Source NHS GMS was added to SMAD3. Rating Changed from Green List (high evidence) to Green List (high evidence)

25 Jul 2017, Gel status: 4

panel promoted to version 1

Louise Daugherty (Genomics England Curator)

25 July 2017 Panel reviews were assessed, and panel was revised according to reviews and further curation.

26 Apr 2017, Gel status: 4

Upload gene information

Louise Daugherty (Genomics England Curator)

SMAD3 was added to Ehlers-Danlos syndromespanel. Sources: Illumina TruGenome Clinical Sequencing Services

26 Apr 2017, Gel status: 4

Gene classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

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

26 Apr 2017, Gel status: 1

Set Mode of Inheritance

Louise Daugherty (Genomics England Curator)

Mode of inheritance for SMAD3 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

26 Apr 2017, Gel status: 1

Set publications

Louise Daugherty (Genomics England Curator)

Publications for SMAD3 were set to 21217753;21778426;22167769

26 Apr 2017, Gel status: 1

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for SMAD3 were set to Loeys-Dietz syndrome 3, 613795

24 Jan 2017, Gel status: 0

Created

Ellen McDonagh (Genomics England Curator)

SMAD3 was created by ellenmcdonagh

24 Jan 2017, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

SMAD3 was added to Ehlers-Danlos syndromespanel. Sources: Emory Genetics Laboratory,Expert list