Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: TMC8

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

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

Green List (high evidence)

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.

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.