Thoracic aortic aneurysm or dissection

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

Louise Daugherty (Genomics England Curator)

As a result of watchlist tag audit the watchlist tag was removed from SMAD2- this is now a green gene with sufficient evidence/review
Created: 13 Jan 2020, 4:51 p.m. | Last Modified: 13 Jan 2020, 4:51 p.m.
Panel Version: 1.112

Rebecca Whittington (South West GLH)

Green List (high evidence)

No OMIM association; HGMD Loeys-Dietz syndrome
Created: 25 Mar 2019, 4:30 p.m.
Schepers et al 2018 Hum Mutat 39:621 PMID:29392890 review variants in TGFB2/3 and SMAD2/3 in LDS, listing 6 likely pathogenic variants from this and previous studies. All missense variants to date
Created: 25 Mar 2019, 4:27 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

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

Ellen McDonagh (Genomics England Curator)

I don't know

This gene was part of an initial gene list collated by Matthew Edwards Royal Brompton Hospital sent 16th Jan 2019 on behalf of the London South GLH for review by the GMS Cardiology Specialist Group. Only gene symbol from the Royal Brompton gene panel was provided - suggested initial gene rating and evidence for inclusion not provided with the list.
Created: 20 Feb 2019, 2:17 p.m.

Helen Brittain (Genomics England Curator)

Green List (high evidence)

Comment when marking as ready: Meets evidence criteria in terms of three unrelated families reported. Only a single paper to date therefore tagged as watchlist in case further evidence emerges to the contrary. To be reviewed in the light of any new evidence.
Created: 26 Jul 2017, 8:44 a.m.
Comment on mode of pathogenicity: Missense variation reported to date. Some evidence to suggest upregulation of SMAD2. Further cases required to confirm scope of causative variation
Created: 26 Jul 2017, 8:43 a.m.
Comment on list classification: Meets evidence criteria - three unrelated families reported
Created: 26 Jul 2017, 8:41 a.m.
PMID 26247889 contains information about three unrelated cases with vascular disease, identified to have sequence variants in SMAD2. These are all missense variants, consdered to be pathogenic, with evidence of involvement in TGFbeta signalling and increased expression of SMAD2. I cannot find any contradictory evidence. The clinical phenotypes are an appropriate fit for this panel, however the evidence to date suggests that this is likely to be a relatively rare cause (3 from a cohort of 365).
Created: 26 Jul 2017, 8:36 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Arterial aneurysms and dissections

Publications

Mode of pathogenicity
Other

Rebecca Foulger (Genomics England curator)

PMID:26247899 (2015) report 3 families with arterial aneurysms and dissections with pathogenic variants in SMAD2:
Patient P1-1: c.1346T>C, p.(Leu449Ser). Patient P2-1: c.1369G>A, p.(Gly457Arg) de novo variant. Patients P3-1 and P3-2 (affected siblings): c.1163A>G, p.(Gln388Arg).
Created: 25 Jul 2017, 3 p.m.
Added SMAD2 to panel as advised by reviewer of the Ehlers-Danlos syndrome (EDS) panel, Neeti Ghali, and Fleur Van Dijk (author of PMID:26247899).
Created: 25 Jul 2017, 3 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
arterial aneurysms and dissections

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • South West GLH
  • London South GLH
  • Expert Review Green
  • Other
Phenotypes
  • arterial aneurysms and dissections
OMIM
601366
Clinvar variants
Variants in SMAD2
Penetrance
Complete
Publications
Mode of Pathogenicity
Other - please provide details in the comments
Panels with this gene

History Filter Activity

13 Jan 2020, Gel status: 3

Removed Tag

Louise Daugherty (Genomics England Curator)

Tag watchlist was removed from gene: SMAD2.

21 Feb 2019, Gel status: 4

Added New Source, Set mode of inheritance

Ellen McDonagh (Genomics England Curator)

Source South West GLH was added to SMAD2. Mode of inheritance for gene SMAD2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

20 Feb 2019, Gel status: 3

Added New Source, Status Update

Ellen McDonagh (Genomics England Curator)

Source London South GLH was added to SMAD2. Rating Changed from Green List (high evidence) to Green List (high evidence)

26 Jul 2017, Gel status: 4

Gene classified by Genomics England curator

Helen Brittain (Genomics England Curator)

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

26 Jul 2017, Gel status: 4

Set mode of pathogenicity

Helen Brittain (Genomics England Curator)

Mode of pathogenicity for SMAD2 was changed to Other - please provide details in the comments

26 Jul 2017, Gel status: 4

Gene classified by Genomics England curator

Helen Brittain (Genomics England Curator)

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

25 Jul 2017, Gel status: 0

Created

Rebecca Foulger (Genomics England curator)

SMAD2 was created by rfoulger

25 Jul 2017, Gel status: 0

Added New Source

Rebecca Foulger (Genomics England curator)

SMAD2 was added to Familial Thoracic Aortic Aneurysm Diseasepanel. Sources: Other