Skeletal dysplasia
Gene: SMAD6EnsemblGeneIds (GRCh38): ENSG00000137834
EnsemblGeneIds (GRCh37): ENSG00000137834
OMIM: 602931, Gene2Phenotype
SMAD6 is in 9 panels
3 reviews
Eleanor Williams (Genomics England Curator)
The rating of this gene has been updated following NHS Genomic Medicine Service approval.Created: 6 Mar 2022, 5:41 p.m. | Last Modified: 6 Mar 2022, 5:41 p.m.
Panel Version: 2.176
Ivone Leong (Genomics England Curator)
Comment on list classification: New gene added by Tracy Lester (Genetics laboratory, Oxford UK). This gene is associated with a phenotype in OMIM and Gene2Phenotype.
Based on the available evidence it is recommended that this gene be given Green status at the next review.Created: 1 Feb 2021, 11:33 a.m. | Last Modified: 1 Feb 2021, 11:33 a.m.
Panel Version: 2.81
Tracy Lester (Genetics laboratory, Oxford UK)
SMAD6 is frequently mutated in non-syndromic radioulnar synostosis.Using exome seq the authors found 16 LOF and 6 rare missense variants in sporadic cases, which was a highly significant association. The findings were replicated in a different cohort. Four cases had de novo variants and others were inherited in a dominant fashion.
SMAD6 LOF variants have also been shown to be enriched in mid-line craniosynostosis and in certain cardiac disorders. It isn't yet clear if a variant can cause different phenotypes in the same family or combinations of these phenotypes in the same individual. Genotype-phenotype correlation is not understood.
This gene is currently tested diagnostically in cases of mid-line craniosynostosis and is green on panel R100.
Sources: NHS GMSCreated: 30 Jan 2021, 10:03 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Radioulnar synostosis
Publications
Details
- Mode of Inheritance
- MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
- Sources
-
- Expert Review Green
- Phenotypes
-
- {Radioulnar synostosis, nonsyndromic}, OMIM:179300
- OMIM
- 602931
- Clinvar variants
- Variants in SMAD6
- Penetrance
- Incomplete
- Publications
- Panels with this gene
-
- Thoracic aortic aneurysm or dissection (GMS)
- Rare syndromic craniosynostosis or isolated multisuture synostosis
- Familial non syndromic congenital heart disease
- Syndromic and non syndromic craniosynostosis involving midline sutures
- Thoracic aortic aneurysm or dissection
- Limb disorders
- Fetal anomalies
- DDG2P
- Skeletal dysplasia
History Filter Activity
Set Phenotypes
Eleanor Williams (Genomics England Curator)Phenotypes for gene: SMAD6 were changed from Radioulnar synostosis to {Radioulnar synostosis, nonsyndromic}, OMIM:179300
Removed Tag
Eleanor Williams (Genomics England Curator)Tag for-review was removed from gene: SMAD6.
Added New Source, Status Update
Eleanor Williams (Genomics England Curator)Source Expert Review Green was added to SMAD6. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Entity classified by Genomics England curator
Ivone Leong (Genomics England Curator)Gene: smad6 has been classified as Amber List (Moderate Evidence).
Added Tag
Ivone Leong (Genomics England Curator)Tag for-review tag was added to gene: SMAD6.
Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes, Set penetrance
Tracy Lester (Genetics laboratory, Oxford UK)gene: SMAD6 was added gene: SMAD6 was added to Skeletal dysplasia. Sources: NHS GMS Mode of inheritance for gene: SMAD6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SMAD6 were set to 31138930 Phenotypes for gene: SMAD6 were set to Radioulnar synostosis Penetrance for gene: SMAD6 were set to Incomplete Review for gene: SMAD6 was set to GREEN