Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: NLRC4Comment 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, 1:36 p.m. | Last Modified: 14 Oct 2020, 1:36 p.m.
Panel Version: 2.285
The following PubMed IDs were added to entity NLRC4: 25385754. These publications have been associated with OMIM phenotype MIM#616115, which is listed for this entity, by the autoinflammation 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
The following PubMed IDs were added to entity NLRC4: 25217960;25217959. These publications have been associated with OMIM phenotype MIM#616050, which is listed for this entity, by the autoinflammation 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, 9:33 a.m. | Last Modified: 13 Oct 2020, 9:33 a.m.
Panel Version: 2.207
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
Comment on list classification: Associated with phenotype in OMIM and not in Gen2Phen. At least 3 variants identified in unrelated cases (2 in 3 cases of Autoinflammation with infantile enterocolitis 616050 and 1 in a case of ?Familial cold autoinflammatory syndrome 4 616115). All were reported as gain of function variants, with functional studies to support this view.Created: 2 May 2018, 3:37 p.m.
Comment on mode of pathogenicity: Autoinflammation with infantile enterocolitis 616050 and Familial cold autoinflammatory syndrome 4 616115 are associated by gain of function variants in NLRC4, which result in activation of CASP1.Created: 2 May 2018, 3:28 p.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
OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): NLRC4 .PanelApp HGNC gene symbol check: NLRC4 . IUIS Disease: NLRC4-MAS (macrophage activating syndrome) or familial cold autoinflammatory syndrome 4 . IUIS Inheritance: AD GOF .T cells: N/A, .B cells: N/A, .IUIS Other affected cells: PMNs monocytes macrophages. IUIS Associated features: Severe enterocolitis and macrophage activation syndrome. IUIS Major category: Autoinflammatory Disorders. IUIS Subcategory: Defects Affecting the InflammasomeCreated: 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: 20 Apr 2018, 12:25 p.m.
Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: NLRC4, GRID_Gene_Symbol: NLRC4, GRID_Transcript_ENS_Community submitted: ENST00000404025, GRID_Transcript_RefSeq: NM_021209.4, GRID_Transcript_ENS_used_on_Production: ENST00000404025Created: 17 Apr 2018, 12:12 p.m.
Phenotypes for gene: NLRC4 were changed from ?Familial cold autoinflammatory syndrome 4 616115; Autoinflammation with infantile enterocolitis 616050; Severe enterocolitis and macrophage activation syndrome; Autoinflammatory Disorders to Autoinflammation with infantile enterocolitis, OMIM:616050; ?Familial cold autoinflammatory syndrome 4, OMIM:616115; Severe enterocolitis and macrophage activation syndrome; Autoinflammatory Disorders
Gene: nlrc4 has been classified as Green List (High Evidence).
Publications for gene NLRC4 were updated from 27876626; 25217959; 25385754; 25217960 to 27876626; 25217959; 25385754; 25217960
Source Other was added to NLRC4. Publications for gene NLRC4 were updated from 25217960; 25217959; 25385754; 27876626 to 27876626; 25217959; 25385754; 25217960 Rating Changed from Green List (high evidence) to Red List (low evidence)
Source NHS GMS was added to NLRC4.
Source North West GLH was added to NLRC4.
Source London North GLH was added to NLRC4.
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.
Phenotypes for gene NLRC4 were set to ?Familial cold autoinflammatory syndrome 4 616115, Autoinflammation with infantile enterocolitis 616050, Severe enterocolitis and macrophage activation syndrome, Autoinflammatory Disorders
IUIS Classification February 2018 was added to NLRC4. Panel: Primary immunodeficiency disorders
Victorian Clinical Genetics Services was added to NLRC4. Panel: Primary immunodeficiency disorders
Gene: nlrc4 has been classified as Green List (High Evidence).
This gene has been classified as Green List (High Evidence).
Mode of pathogenicity for NLRC4 was changed to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Publications for NLRC4 were set to 25217960; 25217959; 25385754; 27876626
Publications for NLRC4 were set to 25217960; 25217959; 25385754
Phenotypes for NLRC4 were set to ?Familial cold autoinflammatory syndrome 4 616115; Autoinflammation with infantile enterocolitis 616050
Phenotypes for NLRC4 were set to Familial cold autoinflammatory syndrome 4; Autoinflammation with infantile enterocolitis
Expert Review Amber was added to NLRC4. Panel: Primary immunodeficiency disorders
Phenotypes for gene NLRC4 were set to Familial cold autoinflammatory syndrome 4, Autoinflammation with infantile enterocolitis, Autoinflammation with infantile enterocolitis
NLRC4 was added to Primary immunodeficiency disorders panel. Sources: GRID V2.0
NLRC4 was created by Louise Daugherty