Hereditary haemorrhagic telangiectasia

Gene: EPHB4

Green List (high evidence)

EPHB4 (EPH receptor B4)
EnsemblGeneIds (GRCh38): ENSG00000196411
EnsemblGeneIds (GRCh37): ENSG00000196411
OMIM: 600011, Gene2Phenotype
EPHB4 is in 8 panels

4 reviews

Matthew Edwards (Clinical Genetics & Genomics Lab, Royal Brompton & Harefield NHS Trust)

Green List (high evidence)

On CGGL Royal Brompton HHT diagnostic panel. Pathogenic variants are a cause of Capillary malformation-arteriovenous malformation 2, a differential diagnosis of HHT
Created: 22 Sep 2019, 8:03 p.m. | Last Modified: 22 Sep 2019, 8:03 p.m.
Panel Version: 1.51

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

Phenotypes
OMIM: 618196 Capillary malformation-arteriovenous malformation 2; 617300 Lymphatic malformation 7

Publications

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

Louise Daugherty (Genomics England Curator)

Comment on list classification: Changed from Amber to Green. Appropriate phenotype, sufficient cases and external expert review all support gene-disease association and relevance to this panel to rate gene as Green.
Created: 27 Jun 2019, 10:53 a.m. | Last Modified: 27 Jun 2019, 10:53 a.m.
Panel Version: 1.49
Comment on phenotypes: Added phenotypes suggested from expert review that indicate relevance to inclusion on the Hereditary haemorrhagic telangiectasia panel
Created: 27 Jun 2019, 10:48 a.m. | Last Modified: 27 Jun 2019, 10:48 a.m.
Panel Version: 1.47
Comment on publications: Added PMID: 30760892 from external reviewer to support upgrading of gene to Green
Created: 27 Jun 2019, 10:46 a.m. | Last Modified: 27 Jun 2019, 10:46 a.m.
Panel Version: 1.46

Claire Shovlin (Imperial College London)

Green List (high evidence)

Emerging as an HHT diagnostic mimic in patients sequenced through 100K with "HHT-like" telangiectasia. Note the syndrome is termed Capillary Malformation-Arteriovenous Malformation (CM-AVM2, PMID: 30760892) but a pathogenic EPHB4 variant was also identified in seven unrelated ENG/ACVRL1/SMAD4 negative cases presenting with features that might be considered suspicious of HHT (epistaxis, telangiectasia, [with significant differences in cutaneous presentation to HHT] and occasional cerebral malformations, PMID: 28687708).
Created: 24 Jun 2019, 12:35 a.m. | Last Modified: 24 Jun 2019, 12:35 a.m.
Panel Version: 1.44

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

Phenotypes
capillary malformation, epistaxis, telangiectasia, cerebral AVM

Publications

Ellen Thomas (Genomics England Curator)

I don't know

At least one family in 100k recruited under HHT has a mutation in this gene as it's an overlap condition. Consider whether to include with the GLH specialist group for GMS diagnostic analysis.
Sources: Other
Created: 21 Jun 2019, 12:26 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Capillary malformation-arteriovenous malformation 2; 618196

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
Phenotypes
  • Capillary malformation-arteriovenous malformation 2, 618196
  • Capillary malformation, epistaxis, telangiectasia, cerebral AVM
OMIM
600011
Clinvar variants
Variants in EPHB4
Penetrance
Incomplete
Publications
Panels with this gene

History Filter Activity

31 Jul 2019, Gel status: 3

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: EPHB4 were changed from Capillary malformation-arteriovenous malformation 2; 618196; Capillary malformation, epistaxis, telangiectasia, cerebral AVM to Capillary malformation-arteriovenous malformation 2, 618196; Capillary malformation, epistaxis, telangiectasia, cerebral AVM

27 Jun 2019, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: ephb4 has been classified as Green List (High Evidence).

27 Jun 2019, Gel status: 2

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: EPHB4 were changed from Capillary malformation-arteriovenous malformation 2; 618196; capillary malformation, epistaxis, telangiectasia, cerebral AVM to Capillary malformation-arteriovenous malformation 2; 618196; Capillary malformation, epistaxis, telangiectasia, cerebral AVM

27 Jun 2019, Gel status: 2

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: EPHB4 were changed from Capillary malformation-arteriovenous malformation 2; 618196 to Capillary malformation-arteriovenous malformation 2; 618196; capillary malformation, epistaxis, telangiectasia, cerebral AVM

27 Jun 2019, Gel status: 2

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: EPHB4 were set to 28687708; 28730721

27 Jun 2019, Gel status: 2

Set mode of inheritance

Louise Daugherty (Genomics England Curator)

Mode of inheritance for gene: EPHB4 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

21 Jun 2019, Gel status: 2

Entity classified by Genomics England curator

Ellen Thomas (Genomics England Curator)

Gene: ephb4 has been classified as Amber List (Moderate Evidence).

21 Jun 2019, Gel status: 1

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes, Set penetrance

Ellen Thomas (Genomics England Curator)

gene: EPHB4 was added gene: EPHB4 was added to Hereditary haemorrhagic telangiectasia. Sources: Other Mode of inheritance for gene: EPHB4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: EPHB4 were set to 28687708; 28730721 Phenotypes for gene: EPHB4 were set to Capillary malformation-arteriovenous malformation 2; 618196 Penetrance for gene: EPHB4 were set to Incomplete Review for gene: EPHB4 was set to AMBER