Hereditary haemorrhagic telangiectasia

Gene: ENG

Green List (high evidence)

ENG (endoglin)
EnsemblGeneIds (GRCh38): ENSG00000106991
EnsemblGeneIds (GRCh37): ENSG00000106991
OMIM: 131195, Gene2Phenotype
ENG is in 10 panels

5 reviews

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

Green List (high evidence)

On CGGL Royal Brompton HHT diagnostic panel. Extensive literature evidence
Created: 22 Sep 2019, 7:54 p.m. | Last Modified: 22 Sep 2019, 7:54 p.m.
Panel Version: 1.51

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

Phenotypes
OMIM: 187300 Telangiectasia, hereditary hemorrhagic, type 1

Publications

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

Ian Berry (Leeds Genetics Laboratory)

Green List (high evidence)

Please note for diagnostic applications that upstream promoter variants have been repeatedly described in this gene and diagnostic panels should cover at least to c.-130. The c.-127C>T variant is described in PMID 22192717, 21967607 , 28989145, others at -10 and -58 also described.
Created: 18 Jan 2019, 5:22 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

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

Louise Daugherty (Genomics England Curator)

Green List (high evidence)

Comment on phenotypes: added phenotypes suggested by expert reviewer
Created: 21 Jan 2019, 12:02 p.m.
Comment on publications: Added publications suggested by Ian Berry ( GMS Respiratory Specialist Test Group ) that support gene-disease association and rating of this gene to Green.
Created: 21 Jan 2019, noon
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 ENG; Suggested initial gene rating: Green; Evidence for inclusion: OMIM HHT gene; Evidence for exclusion: none given; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): Multiple promoter/UTR mutations, needs to be covered.
Created: 6 Dec 2018, 12:36 p.m.

Sarah Leigh (Genomics England Curator)

Comment when marking as ready: Associated with phenotype in OMIM, not in G2P / DD. At least 9 variants reported
Created: 12 Dec 2016, 11:39 a.m.
Comment on phenotypes: The following HPO terms provided by Claire Shovlin: Epistaxis (HP:0000421); Nasal mucosa telangiectasia (HP:0000434); Lip telangiectasia (HP:0000214); Tongue telangiectasia (HP:0000227); Palate telangiectasia (HP:0002707) Finger pad telangiectasia (pulp not nail side); Gastrointestinal telangiectasia (HP:0002604); Arteriovenous malformation (HP:0100026); Cerebral arteriovenous malformation (HP:0002408); Pulmonary arteriovenous malformation (HP:0006548); Hepatic arteriovenous malformation (HP:0006574) Spinal arteriovenous malformation (HP:0002390). Additional phenotypes secondary to these diagnostic criteria.
Created: 12 Dec 2016, 11:39 a.m.

Claire Shovlin (Imperial College London)

Green List (high evidence)

OMIM #187300 (HHT type 1, PMID 7894484)
Phenotypic differences to HHT type 2 due to ACVRL1, particularly frequency of hepatic, pulmonary and cerebral AVMs (PMID: 16155196), and lower prevalence of pulmonary arterial hypertension (PMID: 14684682)
ExAc Constraint metrics [http://biorxiv.org/content/early/2016/05/10/030338 ] identify ENG as a loss-of-function (LOF) intolerant gene, with better toleration of missense substitutions than ACVRL1 : Loss of function ENG expected 22.3, observed 2, pLI =0.99. Synonymous ENG expected number of ExAc variants123.3, observed 121, z=0.13. Missense ENG expected 235.9, observed 223, z=0.41 (contrast ACVRL1 expected 199.6, observed 132 z=2.34).
Created: 13 Nov 2016, 9:54 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Epistaxis (HP:0000421); Nasal mucosa telangiectasia (HP:0000434); Lip telangiectasia (HP:0000214); Tongue telangiectasia (HP:0000227); Palate telangiectasia (HP:0002707) Finger pad telangiectasia (pulp not nail side); Gastrointestinal telangiectasia (HP:0002604); Arteriovenous malformation (HP:0100026); Cerebral arteriovenous malformation (HP:0002408); Pulmonary arteriovenous malformation (HP:0006548); Hepatic arteriovenous malformation (HP:0006574) Spinal arteriovenous malformation (HP:0002390). Additional phenotypes secondary to these diagnostic criteria.

Publications

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

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Eligibility statement prior genetic testing
  • Expert Review Green
  • Emory Genetics Laboratory
  • UKGTN
  • Radboud University Medical Center, Nijmegen
  • UKGTN
  • Emory Genetics Laboratory
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Telangiectasia, hereditary hemorrhagic, type 1, 187300
  • Epistaxis (HP:0000421)
  • Nasal mucosa telangiectasia (HP:0000434)
  • Lip telangiectasia (HP:0000214)
  • Tongue telangiectasia (HP:0000227)
  • Palate telangiectasia (HP:0002707)
  • Finger pad telangiectasia (pulp not nail side)
  • Gastrointestinal telangiectasia (HP:0002604)
  • Arteriovenous malformation (HP:0100026)
  • Cerebral arteriovenous malformation (HP:0002408)
  • Pulmonary arteriovenous malformation (HP:0006548)
  • Hepatic arteriovenous malformation (HP:0006574
  • )
  • Spinal arteriovenous malformation (HP:0002390)
OMIM
131195
Clinvar variants
Variants in ENG
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

21 Jan 2019, Gel status: 4

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: ENG were changed from Telangiectasia, hereditary hemorrhagic, type 1 187300 to Telangiectasia, hereditary hemorrhagic, type 1, 187300; Epistaxis (HP:0000421); Nasal mucosa telangiectasia (HP:0000434); Lip telangiectasia (HP:0000214); Tongue telangiectasia (HP:0000227); Palate telangiectasia (HP:0002707); Finger pad telangiectasia (pulp not nail side); Gastrointestinal telangiectasia (HP:0002604); Arteriovenous malformation (HP:0100026); Cerebral arteriovenous malformation (HP:0002408); Pulmonary arteriovenous malformation (HP:0006548); Hepatic arteriovenous malformation (HP:0006574; ); Spinal arteriovenous malformation (HP:0002390)

21 Jan 2019, Gel status: 4

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: ENG were set to 7894484; 16155196; 14684682

6 Dec 2018, Gel status: 3

Added New Source, Status Update

Louise Daugherty (Genomics England Curator)

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

14 Dec 2016, Gel status: 4

Upload gene information

Ellen McDonagh (Genomics England Curator)

ENG was added to Hereditary haemorrhagic telangiectasiapanel. Sources: Eligibility statement prior genetic testing

12 Dec 2016, Gel status: 4

panel promoted to version 1

Sarah Leigh (Genomics England Curator)

Promoted to V1 (12th December 2016)

12 Dec 2016, Gel status: 4

Gene classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

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

12 Dec 2016, Gel status: 6

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for ENG were set to Telangiectasia, hereditary hemorrhagic, type 1 187300

12 Dec 2016, Gel status: 6

Set publications

Sarah Leigh (Genomics England Curator)

Publications for ENG were set to 7894484; 16155196; 14684682

12 Dec 2016, Gel status: 6

Set Mode of Inheritance

Sarah Leigh (Genomics England Curator)

Mode of inheritance for ENG was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

19 Nov 2015, Gel status: 6

Added New Source

Ellen McDonagh (Genomics England Curator)

ENG was added to Hereditary haemorrhagic telangiectasiapanel. Source: Illumina TruGenome Clinical Sequencing Services

30 Oct 2015, Gel status: 4

Added New Source

Ellen McDonagh (Genomics England Curator)

ENG was added to Hereditary haemorrhagic telangiectasiapanel. Source: UKGTN

30 Oct 2015, Gel status: 3

Added New Source

Ellen McDonagh (Genomics England Curator)

ENG was added to Hereditary haemorrhagic telangiectasiapanel. Source: Emory Genetics Laboratory

30 Oct 2015, Gel status: 2

Set Mode of Inheritance, Added New Source

Ellen McDonagh (Genomics England Curator)

ENG was added to Hereditary haemorrhagic telangiectasiapanel. Source: Illumina TruGenome Clinical Sequencing Services Model of inheritance for gene ENG was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

30 Oct 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

ENG was added to Hereditary haemorrhagic telangiectasiapanel. Source: Radboud University Medical Center, Nijmegen

30 Oct 2015, Gel status: 0

Created

Ellen McDonagh (Genomics England Curator)

ENG was created by ellenmcdonagh

30 Oct 2015, Gel status: 0

Added New Source

Ellen McDonagh (Genomics England Curator)

ENG was added to Hereditary haemorrhagic telangiectasiapanel. Sources: Eligibility statement prior genetic testing