Pneumothorax - familial

Gene: SMAD2

Amber List (moderate evidence)

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

2 reviews

Helen Brittain (Genomics England Curator)

I don't know

Missense variants reported in Loeys-Dietz syndrome, for which there are sufficient cases. Increased SMAD2 expression noted in bullae from patients who have had pneumothoraces. I cannot find clear evidence of individuals with SMAD2 pathogenic variants who have had pneumothoraces, although there are relatively small numbers of cases reported.
Created: 18 Jan 2019, 2:27 p.m.

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

Phenotypes
Loeys-Dietz syndrome

Publications

Mode of pathogenicity
Other

Louise Daugherty (Genomics England Curator)

I don't know

October 2019: Gene flagged up for further discussion by Respiratory Test Group regarding the inclusion of genes associated with Loeys-Dietz syndrome and classical EDS. However, no additional feedback was received, so gene will not be upgraded to Green as inclusion on this panel remains unclear. COL5A1, SMAD2 and SMAD3 are rated Green on the R101 Ehlers Danlos syndromes panel https://panelapp.genomicsengland.co.uk/panels/53/
Created: 5 Nov 2019, 2:56 p.m. | Last Modified: 5 Nov 2019, 2:56 p.m.
Panel Version: 1.18
Comment on phenotypes: added phenotype as suggested by clinical team
Created: 21 Jan 2019, 12:15 p.m.
Comment on publications: Added publications suggested by expert clinical review that support Loeys-Dietz syndrome; pneumothorax a common feature.
Created: 21 Jan 2019, 12:14 p.m.
Comment on mode of inheritance: added MOI from review
Created: 21 Jan 2019, 12:12 p.m.
Comment on list classification: changed to Amber from Red - awaiting confirmation from GMS Respiratory Specialist Test Group- is pneumothorax part of the phenotype for LDS caused by variants in SMAD2
Created: 21 Jan 2019, 12:12 p.m.
From GMS Respiratory Specialist Test Group webex call 18th Jan 2019: Loeys-Dietz syndrome - is pneumothorax part of the phenotype for LDS caused by variants in these genes? Specialist group to contact Stefan Marciniak/Bart Loeys to confirm this
Created: 21 Jan 2019, 10:39 a.m.
Initial gene list and info collated by Ian Berry Leeds Genetics Laboratory November 2018 on behalf of the GMS Respiratory specialist test group. Gene Symbol submitted: SMAD2; Suggested initial gene rating: Green; Evidence for inclusion: Loeys-Dietz syndrome; pneumothorax a common feature. New gene not on PanelApp, see PMID 29392890 & 26247899.; Evidence for exclusion: none given; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none given
Created: 6 Dec 2018, 2:37 p.m.

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Amber
  • NHS GMS
Phenotypes
  • Loeys-Dietz syndrome,MONDO:0018954
OMIM
601366
Clinvar variants
Variants in SMAD2
Penetrance
None
Publications
Mode of Pathogenicity
Other
Panels with this gene

History Filter Activity

17 Mar 2021, Gel status: 2

Set Phenotypes

Ivone Leong (Genomics England Curator)

Phenotypes for gene: SMAD2 were changed from Loeys-Dietz syndrome to Loeys-Dietz syndrome,MONDO:0018954

21 Jan 2019, Gel status: 2

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: SMAD2 were changed from to Loeys-Dietz syndrome

21 Jan 2019, Gel status: 2

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: SMAD2 were set to

21 Jan 2019, Gel status: 2

Set mode of pathogenicity

Louise Daugherty (Genomics England Curator)

Mode of pathogenicity for gene: SMAD2 was changed from to Other

21 Jan 2019, Gel status: 2

Set mode of inheritance

Louise Daugherty (Genomics England Curator)

Mode of inheritance for gene: SMAD2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

21 Jan 2019, Gel status: 2

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: smad2 has been classified as Amber List (Moderate Evidence).

6 Dec 2018, Gel status: 1

Created, Added New Source, Set mode of inheritance

Louise Daugherty (Genomics England Curator)

gene: SMAD2 was added gene: SMAD2 was added to Pneumothorax - familial. Sources: NHS GMS Mode of inheritance for gene: SMAD2 was set to