Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: ICOSComment 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, 12:57 p.m. | Last Modified: 14 Oct 2020, 12:57 p.m.
Panel Version: 2.254
The following PubMed IDs were added to gene ICOS (OMIM gene MIM#604558): 12577056;28861081. 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
agree with green geneCreated: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
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
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): ICOS .PanelApp HGNC gene symbol check: ICOS . IUIS Disease: ICOS deficiency . IUIS Inheritance: AR .T cells: N/A, .B cells: Normal, .IUIS Other affected cells: N/A. IUIS Associated features: Recurrent infections, autoimmunity, gastroenteritis, granulomas . IUIS Major category: Immunodeficiencies affecting cellular and humoral immunity. IUIS Subcategory: Combined Immunodeficiencies Generally Less Profound than Severe Combined ImmunodeficiencyCreated: 2 Jul 2018, 10:35 a.m.
Comment on list classification: Changed from Amber to Green- enough evidence in the literature and external expert reivewCreated: 18 Jun 2018, 11:06 a.m.
No longer deemed founder-effect since the Salzer et al. (2004) publication, other variants (all deletions) have been observed and in other ethnicities (PMID: 29867948). Schepp et all (2017) PMID:28861081 reviewed seven families’ pedigrees. The inheritance was strictly autosomal-recessive in all families, and all mutations led to a failure to detect the protein on the surface of activated T-cells. Families 1-4 had a homozygous deletion of a 1,815 base pair region including exon 2, intron 2, exon 3, and parts of intron 3 of the ICOS gene (c.126-568.del) (PMID:12577056, 15507387). This out of frame deletion led to a premature stop codon and shortened transcript (PMID:12577056). A common ancestor is assumed for these four families. In the unrelated family 5, sequencing of the ICOS gene revealed a homozygous deletion of a T at codon 285, leading to a frameshift and the introduction of a stop codon at amino acid position 121 and resulting in a truncated ICOS transcript (c.285delT) (PMID:19380800). The patients from family 6 from Kuwait were found to carry a single nucleotide homozygous deletion in Exon 2 (c.90delG), leading to a frameshift and premature stop codon in Exon 2 (PMID: 25678089). In the children of the consanguineous family 7, a homozygous 10 base-pair deletion in ICOS (c.321_330del) led to a frameshift and a premature stop after 10 codons in the new reading frame (p.F108YfsX118) (PMID:26399252).Created: 18 Jun 2018, 11:04 a.m.
Clinically, patients present with an increased susceptibility to infections, autoimmune manifestations, and an increased risk of malignancy PMID:10413651.Created: 18 Jun 2018, 10:41 a.m.
from Jung et al. (2018) PMID: 29867948 : To date, homozygous mutations (deletions) in ICOS have been identified in 16 patients, resulting in the absence of ICOS protein on T cells. Following the initial description of this monogenic defect in 2003 (PMID:12577056 ), a number of other patients have been identified worldwide. Of the seven families, three came from Germany (12577056, 15507387), one from Austria (15507387), one from Japan (19380800), one from Kuwait (25678089), and one from UK with Pakistani background (26399252). ICOS deficiency was initially considered as a “predominantly antibody deficiency” by the IUIS PID expert committee (PMID:24795713), but following published patients with more complex phenotypes (28861081), allowed a reclassification of the disease as a CID (PMID:29226302, 29226301).Created: 18 Jun 2018, 10:31 a.m.
In 5 affected individuals from 2 families with CVID due to ICOS deficiency, Salzer et al. (2004) identified the same homozygous deletion in the ICOS gene that was found by Grimbacher et al. (2003). All 4 families were from the same region along the Danube River in Germany and Austria, and haplotype analysis indicated a founder effect.Created: 18 Jun 2018, 10:18 a.m.
added deletion tagCreated: 18 Jun 2018, 10:11 a.m.
Comment on publications: added recent publications PMID:28861081;29867948 to support ICOS deficiency in patients with prominent autoimmune features and opportunistic infection profiles, providing ample evidence that B-cell counts decline during the course of the disease. ICOS deficiency does not just produce isolated hypogammaglobulinemia.Created: 18 Jun 2018, 10:05 a.m.
Comment on publications: added publications suggested from external expert reviewsCreated: 18 Jun 2018, 9:40 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: ICOS, PanelApp HGNC gene symbol check: ICOS, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Predominantly antibody disorders / Hypogammaglobulinemias / Common variable immunodeficiency disorders (CVID); Predominantly antibody disorders / Hypogammaglobulinemias / Isolated IgG subclass deficiencyCreated: 17 Apr 2018, 12:29 p.m.
Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: ICOS, GRID_Gene_Symbol: ICOS, GRID_Transcript_ENS_Community submitted: ENST00000316386, GRID_Transcript_RefSeq: NM_012092.3, GRID_Transcript_ENS_used_on_Production: ENST00000316386Created: 17 Apr 2018, 12:12 p.m.
Reports after the original description show that a CID phenotype is possible (with opportunistic infection, colitis etc)Created: 6 Jan 2017, 2:58 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
hypogammaglobulinaemia, agammaglobulinaemia, combined immunodeficiency
Publications
Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Comment when marking as ready: No expert reviews. No association with disease on Gen2Phen. Two publications reporting a defined deletion of exons 2-3 in 9 members of 4 families, haplotype analysis reveals founder effectCreated: 11 May 2016, 8:30 a.m.
Gene: icos has been classified as Green List (High Evidence).
Source Other was added to ICOS. Publications for gene ICOS were updated from 29867948; 28861081; 12577056; 15507387; 19380800; 25678089; 26399252; 10413651; 29867948; 25678089; 24795713; 29226302; 29226301 to 10413651; 26399252; 25678089; 29226301; 19380800; 28861081; 15507387; 24795713; 12577056; 29226302; 29867948 Rating Changed from Green List (high evidence) to Red List (low evidence)
Source NHS GMS was added to ICOS.
Source North West GLH was added to ICOS.
Source London North GLH was added to ICOS.
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: icos has been classified as Green List (High Evidence).
Phenotypes for gene ICOS were set to Immunodeficiency, common variable, 1, Immunodeficiency, common variable, 1, 607594, Common variable immunodeficiency disorders (CVID), Isolated IgG subclass deficiency, hypogammaglobulinaemia, gammaglobulinaemia, combined immunodeficiency, Recurrent infections, autoimmunity, gastroenteritis, granulomas, Immunodeficiencies affecting cellular and humoral immunity
IUIS Classification February 2018 was added to ICOS. Panel: Primary immunodeficiency disorders
Victorian Clinical Genetics Services was added to ICOS. Panel: Primary immunodeficiency disorders
Publications for gene: ICOS were set to 29867948; 28861081; 12577056; 15507387; 19380800; 25678089; 26399252; 10413651; 29867948; 25678089; 24795713; 29226302; 29226301
Gene: icos has been classified as Green List (High Evidence).
Publications for gene: ICOS were set to 12577056; 15507387; 26399252; 25678089; 28861081; 29867948
Publications for gene: ICOS were set to 12577056; 15507387; 26399252; 25678089
Phenotypes for ICOS were set to Immunodeficiency, common variable, 1; Immunodeficiency, common variable, 1, 607594; Common variable immunodeficiency disorders (CVID); Isolated IgG subclass deficiency; hypogammaglobulinaemia; gammaglobulinaemia; combined immunodeficiency
Expert Review Amber was added to ICOS. Panel: Primary immunodeficiency disorders
ESID Registry 20171117 was added to ICOS. Panel: Primary immunodeficiency disorders Phenotypes for gene ICOS were set to Immunodeficiency, common variable, 1, Immunodeficiency, common variable, 1, 607594, Common variable immunodeficiency disorders (CVID), Isolated IgG subclass deficiency
Phenotypes for gene ICOS were set to Immunodeficiency, common variable, 1, Immunodeficiency, common variable, 1, 607594
GRID V2.0 was added to ICOS. Panel: Primary immunodeficiency disorders Phenotypes for gene ICOS were set to Immunodeficiency, common variable, 1, Immunodeficiency, common variable, 1, 607594
ICOS Source: GOSH PID 20171156 was removed from gene: ICOS
GOSH PID v.8.0 was added to ICOS. Panel: Primary immunodeficiency disorders
GOSH PID 20171156 was added to ICOS. Panel: Primary immunodeficiency disorders
ICOS was added to Primary immunodeficiency disorders panel. Sources: Expert Review Red, A- or hypo-gammaglobulinaemia v1.25
ICOS was created by Louise Daugherty