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Primary immunodeficiency

Gene: TMC8

Green List (high evidence)

TMC8 (transmembrane channel like 8)
EnsemblGeneIds (GRCh38): ENSG00000167895
EnsemblGeneIds (GRCh37): ENSG00000167895
OMIM: 605829, Gene2Phenotype
TMC8 is in 6 panels

5 reviews

Kimberly Gilmour (Great Ormond Street Hopsital)

Green List (high evidence)

agree with green gene
Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94

Tracy Briggs (Manchester Genomic Medicine Centre)

Green List (high evidence)

YES- this is covered on our targeted exome
Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94

Sophie Hambleton (Newcastle University)

Green List (high evidence)

Eleanor Williams (Genomics England Curator)

Comment on phenotypes: Added MIM number to Epidermodysplasia verruciformis phenotype
Created: 19 Jun 2018, 9:34 p.m.
Comment on publications: Added publications relating to the disease PID classification and variants
Created: 19 Jun 2018, 9:33 p.m.
Comment on list classification: Rating this gene green as there are plausible disease-causing mutations in the TMC8 gene in more than 3 families.
Created: 19 Jun 2018, 9:31 p.m.
This gene (also called EVER2) is associated with Epidermodysplasia verruciformis in OMIM. Patients with Epidermodysplasia verruciformis develop flat warts, caused by a specific group of human papillomaviruses (HPV), which may degenerate into nonmelanoma skin cancers. This disease is listed as a primary immune deficiency by the WHO Committee on Primary Immunodeficiency Diseases (Notarangelo et al 2004 (15356576). See Przybyszewska et al (2017) (PMID: 28196644) for a review of its role in immunity. Ramoz et al. (2002)(PMID: 12426567) identified a homozygous deletion of 754 or 755T in the TMC8 gene, which led to a frameshift mutation and termination of the protein at codon 283 in the affected member of an Algerian family with epidermodysplasia verruciformis. They also report that 3 individuals in a consanguineous Colombian family with epidermodysplasia verruciformis had a homozygous 1084G-T transversion in the TMC8 gene that caused a nonsense mutation glu362-to-ter (E362X). Miyauchi et al (2016) (PMID: 26997147) report a Japanese patient with a homozygous 2-bp deletion at the splice site of intron 12 in TMC8, c.1534-3_1534-2delCA, whereas his parents were heterozygous for the mutation. Imahorn et al 2017 (PMID: 28646613) report three Turkish siblings with a homozygous splice site mutation in the donor splice site of IVS9 of TMC8 (c.1127+1G>C) in all patients . Both parentswere heterozygous carriers.
Created: 19 Jun 2018, 9:30 p.m.

Louise Daugherty (Genomics England Curator)

Green List (high evidence)

Gene rating submitted by Kimberly Gilmour and Austen Worth on behalf of London North GLH for the GMS Immunology specialist test group. As discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 and confirmed in follow up email 6th September the Specialist Test Group all agreed there is enough evidence to rate this gene Green.
Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
Gene rating submitted by Tracy Briggs, David Gokhale and Abigal Rousseau on behalf of North West GLH for the GMS Immunology specialist test group. As discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 and confirmed in follow up email on 20th June the Specialist Test Group all agreed there is enough evidence to rate this gene Green.
Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): TMC8 .PanelApp HGNC gene symbol check: TMC8 . IUIS Disease: EVER2 deficiency . IUIS Inheritance: AR .T cells: Variable, but sometimes absent low TRECs, .B cells: N/A, .IUIS Other affected cells: Keratinocytes and leukocytes. IUIS Associated features: HPV (group B1) infections and cancer of the skin (typical EV). IUIS Major category: Defects in Intrinsic and Innate Immunity. IUIS Subcategory: Epidermodysplasia verruciformis (HPV)
Created: 2 Jul 2018, 10:35 a.m.
This gene was absent from the original PanelApp PID panel dataset (review April 2018). However it was listed in external expert immunodeficiency diagnostic gene list(s)
GOSH or GRID. In this combined PID panel, this gene has been rated as AMBER and needs further curational review to assess pertinence prior to v1.
Created: 19 Apr 2018, 12:02 p.m.
Original metadata downloaded from ESID Registry. ESID_Gene_original: TMC8 (gene 2), PanelApp HGNC gene symbol check: TMC8, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Defects in innate immunity / Epidermodysplasia verruciformis / Epidermodysplasia verruciformis
Created: 17 Apr 2018, 12:29 p.m.
Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: TMC8, GRID_Gene_Symbol: TMC8, GRID_Transcript_ENS_Community submitted: ENST00000318430, GRID_Transcript_RefSeq: NM_152468.4, GRID_Transcript_ENS_used_on_Production: ENST00000318430
Created: 17 Apr 2018, 12:12 p.m.

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • NHS GMS
  • North West GLH
  • London North GLH
  • Expert Review Green
  • IUIS Classification February 2018
  • Victorian Clinical Genetics Services
  • ESID Registry 20171117
  • GRID V2.0
Phenotypes
  • Epidermodysplasia verruciformis, 226400
  • HPV (group B1) infections and cancer of the skin (typical EV)
  • Defects in Intrinsic and Innate Immunity
OMIM
605829
Clinvar variants
Variants in TMC8
Penetrance
None
Publications
Panels with this gene

History Filter Activity

17 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to TMC8.

17 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source North West GLH was added to TMC8.

17 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source London North GLH was added to TMC8.

12 Jul 2018, Gel status: 4

Panel promoted to version 1.0

Louise Daugherty (Genomics England Curator)

2018-07-12 Louise Daugherty (Genomics England Curator) promoted panel to v1.0. Reviews were assessed, and panel was revised according to expert reviews and further in-house curation based on PanelApp guidelines. Previous panels (A- or hypo-gammaglobulinaemia, Congenital neutropaenia, Agranulocytosis, Combined B and T cell defect, Inherited complement deficiency and SCID panels) that were merged with this panel, were checked again for any changes/new reviews prior to versioning of this panel, these merged panels are now retired/made internal.

1 Jul 2018, Gel status: 4

Set penetrance

Louise Daugherty (Genomics England Curator)

Phenotypes for gene TMC8 were set to Epidermodysplasia verruciformis, 226400, HPV (group B1) infections and cancer of the skin (typical EV), Defects in Intrinsic and Innate Immunity

27 Jun 2018, Gel status: 4

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: tmc8 has been classified as Green List (High Evidence).

27 Jun 2018, Gel status: 4

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: TMC8 were set to Epidermodysplasia verruciformis, 226400

26 Jun 2018, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

IUIS Classification February 2018 was added to TMC8. Panel: Primary immunodeficiency disorders

26 Jun 2018, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

Victorian Clinical Genetics Services was added to TMC8. Panel: Primary immunodeficiency disorders

19 Jun 2018, Gel status: 3

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: TMC8 were set to Epidermodysplasia verruciformis 226400

19 Jun 2018, Gel status: 3

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: TMC8 were set to 15356576; 28196644; 12426567; 26997147; 28646613

19 Jun 2018, Gel status: 3

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: TMC8 were set to 15356576; 28196644; 12426567; 26997147; 26997147

19 Jun 2018, Gel status: 3

Set mode of inheritance

Eleanor Williams (Genomics England Curator)

Mode of inheritance for gene: TMC8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal

19 Jun 2018, Gel status: 3

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: tmc8 has been classified as Green List (High Evidence).

19 Apr 2018, Gel status: 2

Gene classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

This gene has been classified as Amber List (Moderate Evidence).

17 Apr 2018, Gel status: 1

Added New Source, Set penetrance

Louise Daugherty (Genomics England Curator)

ESID Registry 20171117 was added to TMC8. Panel: Primary immunodeficiency disorders Phenotypes for gene TMC8 were set to Epidermodysplasia verruciformis

17 Apr 2018, Gel status: 1

Set penetrance

Louise Daugherty (Genomics England Curator)

Phenotypes for gene TMC8 were set to Epidermodysplasia verruciformis

17 Apr 2018, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

TMC8 was added to Primary immunodeficiency disorders panel. Sources: GRID V2.0

17 Apr 2018, Gel status: 1

Created

Louise Daugherty (Genomics England Curator)

TMC8 was created by Louise Daugherty