Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: ORAI1Comment on list classification: Changed rating of gene from Red to Green. This gene was rated as Green in v2.208 and incorrectly automatically demoted to Red in v2.209. This was due to a defect in the automatic PanelApp uploading tool when a set of publications was added to the panel with the source ‘Other’, and under certain conditions associated to previous sources listed, resulted in the rating of the gene being automatically changed when it should not have been.Created: 14 Oct 2020, 1:38 p.m. | Last Modified: 14 Oct 2020, 1:38 p.m.
Panel Version: 2.289
The following PubMed IDs were added to gene ORAI1 (OMIM gene MIM#610277): 8814256;7798233;16582901. These publications have been associated with the gene by the immunodeficiencies subgroup of the Human Phenotype Ontology Immune Mediated Disorders Consortium (https://hpo-immune-mediated-disorders.groups.io/g/update) in August 2020.Created: 13 Oct 2020, 9:36 a.m. | Last Modified: 13 Oct 2020, 9:36 a.m.
Panel Version: 2.208
Publications
YES- this is covered on our targeted exomeCreated: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
Comment on list classification: Associated with phenotype in OMIM and not in Gen2Phen. At least 4 variants identified in 3 unrelated cases, together with supportive functional studies.Created: 9 May 2018, 10:35 a.m.
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
Green review as there are sufficient cases with immune dysfunction in biallelic form, from the previous reviews, the previous Red rating was based upon delineation of the specific phenotypes for the specific panels. Therefore, Green rating is suitable for this panel that covers a immune dysfunction, not just SCIDCreated: 10 Jul 2018, 4:10 p.m.
OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): ORAI1 .PanelApp HGNC gene symbol check: ORAI1 . IUIS Disease: ORAI-1 deficiency . IUIS Inheritance: AR .T cells: N/A, .B cells: Normal, .IUIS Other affected cells: N/A. IUIS Associated features: Autoimmunity, EDA, non-progressive myopathy. IUIS Major category: Combined immunodeficiencies with associated or syndromic features. IUIS Subcategory: Calcium Channel DefectsCreated: 2 Jul 2018, 10:35 a.m.
This gene was present in the original PanelApp PID panel dataset (review in April 2018) rated as Red. The gene is present in the 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: Orai1 (TMEM142A), PanelApp HGNC gene symbol check: ORAI1, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Combined immunodeficiencies / Combined immunodeficiency (CID) / Combined immunodeficiencyCreated: 17 Apr 2018, 12:29 p.m.
Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: ORAI1, GRID_Gene_Symbol: ORAI1, GRID_Transcript_ENS_Community submitted: ENST00000330079, GRID_Transcript_RefSeq: NM_032790.3, GRID_Transcript_ENS_used_on_Production: ENST00000330079Created: 17 Apr 2018, 12:12 p.m.
Comment on list classification: After feedback from reviewers, gene should remain on the red list.Created: 20 May 2016, 2:18 p.m.
agree with green geneCreated: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
There are 2 publications with 3 different sets of mutations/families so although rare I would make this an amber which we don't seem to have an option of as we review. I agree with Sophie not so much SCID as CID...Created: 20 Oct 2015, 1:42 p.m.
As stated below, there is good evidence that AR mutations in this gene cause immunodeficiencyCreated: 23 Oct 2019, 6:42 a.m. | Last Modified: 23 Oct 2019, 6:42 a.m.
Panel Version: 1.132
There is good evidence that AR mutations in this gene cause immune dysfunction but not SCIDCreated: 19 Oct 2015, 5:45 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
immunodeficiency, ectodermal dysplasia and myopathy
Publications
Gene: orai1 has been classified as Green List (High Evidence).
Source Other was added to ORAI1. Publications for gene ORAI1 were updated from 16582901; 20004786 to 7798233; 16582901; 8814256; 20004786 Rating Changed from Green List (high evidence) to Red List (low evidence)
Source NHS GMS was added to ORAI1.
Source North West GLH was added to ORAI1.
Source London North GLH was added to ORAI1.
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.
Gene: orai1 has been classified as Green List (High Evidence).
Phenotypes for gene ORAI1 were set to Immunodeficiency 9 612782, T-B+ SCID, immunodeficiency, ectodermal dysplasia and myopathy, Combined immunodeficiency, Autoimmunity, EDA, non-progressive myopathy, Combined immunodeficiencies with associated or syndromic features
IUIS Classification February 2018 was added to ORAI1. Panel: Primary immunodeficiency disorders
Victorian Clinical Genetics Services was added to ORAI1. Panel: Primary immunodeficiency disorders
This gene has been classified as Green List (High Evidence).
Phenotypes for ORAI1 were set to Immunodeficiency 9 612782; T-B+ SCID; immunodeficiency, ectodermal dysplasia and myopathy; Combined immunodeficiency
Expert Review Amber was added to ORAI1. Panel: Primary immunodeficiency disorders
ESID Registry 20171117 was added to ORAI1. Panel: Primary immunodeficiency disorders Phenotypes for gene ORAI1 were set to Immunodeficiency 9, T-B+ SCID, immunodeficiency, ectodermal dysplasia and myopathy, Combined immunodeficiency
Phenotypes for gene ORAI1 were set to Immunodeficiency 9, T-B+ SCID, immunodeficiency, ectodermal dysplasia and myopathy
GRID V2.0 was added to ORAI1. Panel: Primary immunodeficiency disorders Phenotypes for gene ORAI1 were set to Immunodeficiency 9, T-B+ SCID, immunodeficiency, ectodermal dysplasia and myopathy
ORAI1 Source: GOSH PID 20171176 was removed from gene: ORAI1
GOSH PID v.8.0 was added to ORAI1. Panel: Primary immunodeficiency disorders
GOSH PID 20171176 was added to ORAI1. Panel: Primary immunodeficiency disorders Model of inheritance for gene ORAI1 was set to BIALLELIC, autosomal or pseudoautosomal
ORAI1 was added to Primary immunodeficiency disorders panel. Sources: Expert Review Red, SCID v1.6
ORAI1 was created by Louise Daugherty