Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: ADAR

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)

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): ADAR1 .PanelApp HGNC gene symbol check: ADAR . IUIS Disease: ADAR1 deficiency, AGS6 . IUIS Inheritance: AR .T cells: N/A, .B cells: N/A, .IUIS Other affected cells: N/A. IUIS Associated features: Classical AGS, BSN, SP. IUIS Major category: Autoinflammatory Disorders. IUIS Subcategory: Type 1 Interferonopathies

Created: 2 Jul 2018, 10:35 a.m.

Comment on phenotypes: added omim MIMid

Created: 11 May 2018, 10:19 a.m.

Comment on list classification: changed fro Amber to Green

Created: 11 May 2018, 9:52 a.m.

Comment on publications: added publications to support the PID phenotype of auto-inflammation which is relevant to this panel

Created: 11 May 2018, 8:52 a.m.

Type I interferonopathies refers to a recently described set of monogenic diseases in which an upregulation of type I interferons is central to their pathogenesis and covers a spectrum of conditions including Aicardi-Goutières Syndrome (AGS), which is a rare genetic disorder most consistently affecting the brain and the skin. The seven AGS-associated genes encode proteins that are involved in either nucleic acid metabolism, one of which, are variants in the gene ADAR that cause Loss-of-Function (recessive or dominant-negative). Studies of the AGS-related protein like ADAR1, suggest that an inappropriate accumulation of self-derived nucleic acids can induce type I interferon signaling (PMID: 24183309; 27643693;25604658;25769924). The interferon signature appears to be a very good marker of disease and the diagnostic criteria for AGS includes the persistent elevation of mRNA levels of interferon-stimulated gene transcript observed in the peripheral blood of almost all cases of AGS with mutations in TREX1, RNASEH2A, RNASEH2C, SAMHD1, ADAR1 and IFIH1, and in 75% of patients with mutations in RNASEH2B (PMID:24183309)

Created: 10 May 2018, 11:23 a.m.

Comment on mode of inheritance: Added MOI from publications, both AR and AD

Created: 10 May 2018, 8:44 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: 20 Apr 2018, 12:25 p.m.

Original metadata downloaded from ESID Registry. ESID_Gene_original: ADAR1, PanelApp HGNC gene symbol check: ADAR, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Diseases of immune dysregulation / Type 1 interferonopathies / Type 1 interferonopathies

Created: 17 Apr 2018, 12:29 p.m.

Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: ADAR, GRID_Gene_Symbol: ADAR, GRID_Transcript_ENS_Community submitted: ENST00000368474, GRID_Transcript_RefSeq: NM_001111.4, GRID_Transcript_ENS_used_on_Production: ENST00000368474

Created: 17 Apr 2018, 12:12 p.m.