Hereditary haemorrhagic telangiectasia

Gene: SMAD4

Green List (high evidence)

SMAD4 (SMAD family member 4)
EnsemblGeneIds (GRCh38): ENSG00000141646
EnsemblGeneIds (GRCh37): ENSG00000141646
OMIM: 600993, Gene2Phenotype
SMAD4 is in 25 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. Extensive literature evidence. causes combined syndrome of HHT and juvenile polyposis syndrome
Created: 22 Sep 2019, 8:09 p.m. | Last Modified: 22 Sep 2019, 8:09 p.m.
Panel Version: 1.51

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

Phenotypes
OMIM: 175050 Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome

Publications

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

Louise Daugherty (Genomics England Curator)

Green List (high evidence)

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 SMAD4; Suggested initial gene rating: Green; Evidence for inclusion: OMIM Juvenile polyposis & HHT gene; Evidence for exclusion: none given; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none given
Created: 6 Dec 2018, 12:36 p.m.

Sarah Leigh (Genomics England Curator)

Comment when marking as ready: Associated with phenotype in OMIM and as a "Plausible disease-causing mutations within, affecting or encompassing the coding region of a single gene identified in multiple (>3) unrelated cases/families with both a developmental disorder and an incidental (nondevelopmental)" disorder Developmental Disorder Gene / G2P. At least 7 variants reported.
Created: 12 Dec 2016, 11:48 a.m.
Comment on phenotypes: Also associated with Polyposis, juvenile intestinal, 174900; Myhre syndrome, 139210; Pancreatic cancer, somatic 260350.
Additional HPO terms added 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. Juvenile polyposis HP: 0012198; Dilatation ascending aorta HP: 005111
Created: 12 Dec 2016, 11:44 a.m.

Claire Shovlin (Imperial College London)

Green List (high evidence)

OMIM #175050 JUVENILE POLYPOSIS/HEREDITARY HEMORRHAGIC TELANGIECTASIA SYNDROME; JPHT.
Created: 13 Nov 2016, 10 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. Juvenile polyposis HP: 0012198; Dilatation ascending aorta HP: 005111

Publications

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

History Filter Activity

6 Dec 2018, Gel status: 3

Added New Source, Status Update

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to SMAD4. 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)

SMAD4 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 SMAD4 were set to Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, 175050

12 Dec 2016, Gel status: 6

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for SMAD4 were set to Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, 175050; ; Hereditary Hemorrhagic Telangiectasia; Hereditary hemorrhagic telangiectasia (HHT); Juvenile Polyposis/Hereditary Hemorrhagic Telangiectasia Syndrome

12 Dec 2016, Gel status: 6

Set publications

Sarah Leigh (Genomics England Curator)

Publications for SMAD4 were set to 15031030

12 Dec 2016, Gel status: 6

Set Mode of Inheritance

Sarah Leigh (Genomics England Curator)

Mode of inheritance for SMAD4 was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

19 Nov 2015, Gel status: 6

Added New Source

Ellen McDonagh (Genomics England Curator)

SMAD4 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)

SMAD4 was added to Hereditary haemorrhagic telangiectasiapanel. Source: UKGTN

30 Oct 2015, Gel status: 3

Added New Source

Ellen McDonagh (Genomics England Curator)

SMAD4 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)

SMAD4 was added to Hereditary haemorrhagic telangiectasiapanel. Source: Illumina TruGenome Clinical Sequencing Services Model of inheritance for gene SMAD4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

30 Oct 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

SMAD4 was added to Hereditary haemorrhagic telangiectasiapanel. Source: Radboud University Medical Center, Nijmegen

30 Oct 2015, Gel status: 0

Created

Ellen McDonagh (Genomics England Curator)

SMAD4 was created by ellenmcdonagh

30 Oct 2015, Gel status: 0

Added New Source

Ellen McDonagh (Genomics England Curator)

SMAD4 was added to Hereditary haemorrhagic telangiectasiapanel. Sources: Eligibility statement prior genetic testing