Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: NLRP3Comment 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, 1:37 p.m. | Last Modified: 14 Oct 2020, 1:37 p.m.
Panel Version: 2.287
The following PubMed IDs were added to entity NLRP3: 12032915. These publications have been associated with OMIM phenotype MIM#607115, 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 NLRP3: 14476827;14872505;11590390. These publications have been associated with OMIM phenotype MIM#191900, 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
The following PubMed IDs were added to entity NLRP3: 18423104;11590390. These publications have been associated with OMIM phenotype MIM#120100, 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, 9:31 a.m. | Last Modified: 13 Oct 2020, 9:31 a.m.
Panel Version: 2.206
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 phenotypes in OMIM and not in Gen2Phen. At least 4 variants identified in unrelated cases of Familial cold-induced inflammatory syndrome 1 120100. At least 4 variants identified in unrelated cases of Muckle-Wells syndrome 191900, 3 variants in unrelated cases of CINCA and one each in cases of Deafness, autosomal dominant 34, with or without inflammation 617772 and Keratoendothelitis fugax hereditaria 148200. Three cases represent overlapping phenotypes and so there a total of 12 variants have been reported (8th March 2018).Created: 8 May 2018, 4:32 p.m.
Comment on phenotypes: Variants also associated with Keratoendothelitis fugax hereditaria 148200Created: 8 May 2018, 4:19 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): NLRP3 .PanelApp HGNC gene symbol check: NLRP3 . IUIS Disease: Neonatal onset multisystem inflammatory disease (NOMID) or chronic infantile neurologic cutaneous and articular syndrome (CINCA) . IUIS Inheritance: AD GOF .T cells: Decreased T cell proliferation, .B cells: N/A, .IUIS Other affected cells: PMNs, chondrocytes. IUIS Associated features: Neonatal onset rash, chronic meningitis, and arthropathy with fever and inflammation. . IUIS Major category: Autoinflammatory Disorders. IUIS Subcategory: Defects Affecting the Inflammasome. // OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): NLRP3 (also called NALP3 CIAS1 or PYPAF1) .PanelApp HGNC gene symbol check: NLRP3 . IUIS Disease: Muckle-Wells syndrome . IUIS Inheritance: AD GOF .T cells: Lymphopenia, lack of TRECS, absent proliferation in response to antigens, .B cells: N/A, .IUIS Other affected cells: PMNs Monocytes. IUIS Associated features: Urticaria, SNHL, amyloidosis. . IUIS Major category: Autoinflammatory Disorders. IUIS Subcategory: Defects Affecting the Inflammasome.Created: 2 Jul 2018, 10:57 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: CIAS1 (NLRP3), PanelApp HGNC gene symbol check: NLRP3, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Autoinflammatory disorders / CINCA syndrome / CINCA syndrome; Autoinflammatory disorders / Familial cold autoinflammatory syndrome / Familial cold autoinflammatory syndrome; Autoinflammatory disorders / Muckle-Wells syndrome / Muckle-Wells syndromeCreated: 17 Apr 2018, 12:29 p.m.
Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: NLRP3, GRID_Gene_Symbol: NLRP3, GRID_Transcript_ENS_Community submitted: ENST00000336119, GRID_Transcript_RefSeq: NM_004895.4, GRID_Transcript_ENS_used_on_Production: ENST00000336119Created: 17 Apr 2018, 12:12 p.m.
Phenotypes for gene: NLRP3 were changed from CINCA syndrome 607115; Muckle-Wells syndrome 191900; Familial cold autoinflammatory syndrome 1 120100; Deafness, autosomal dominant 34, with or without inflammation 617772; Non-pruritic urticaria, arthritis, chills, fever and leukocytosis after cold exposure; Autoinflammatory Disorders; Neonatal onset rash, chronic meningitis, and arthropathy with fever and inflammation; Urticaria, SNHL, amyloidosis to CINCA syndrome, OMIM:607115; Deafness, autosomal dominant 34, with or without inflammation, OMIM:617772; Familial cold inflammatory syndrome 1, OMIM:120100; Muckle-Wells syndrome, OMIM:191900
Gene: nlrp3 has been classified as Green List (High Evidence).
Publications for gene NLRP3 were updated from 28847925; 12522564; 11590390; 14872505; 14476827; 29366613; 11992256; 12032915; 11687797 to 28847925; 12522564; 11590390; 14872505; 18423104; 14476827; 29366613; 11992256; 12032915; 11687797
Publications for gene NLRP3 were updated from 28847925; 12522564; 29366613; 11992256; 12032915; 11687797 to 28847925; 12522564; 11590390; 14872505; 14476827; 29366613; 11992256; 12032915; 11687797
Source Other was added to NLRP3. Publications for gene NLRP3 were updated from 11687797; 11992256; 12032915; 12522564; 28847925; 29366613 to 28847925; 12522564; 29366613; 11992256; 12032915; 11687797 Rating Changed from Green List (high evidence) to Red List (low evidence)
Source NHS GMS was added to NLRP3.
Source North West GLH was added to NLRP3.
Source London North GLH was added to NLRP3.
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: NLRP3 were set to CINCA syndrome 607115; Muckle-Wells syndrome 191900; Familial cold autoinflammatory syndrome 1 120100; Deafness, autosomal dominant 34, with or without inflammation 617772; Non-pruritic urticaria, arthritis, chills, fever and leukocytosis after cold exposure; Autoinflammatory Disorders; Neonatal onset rash, chronic meningitis, and arthropathy with fever and inflammation; Urticaria, SNHL, amyloidosis
IUIS Classification February 2018 was added to NLRP3. Panel: Primary immunodeficiency disorders
Victorian Clinical Genetics Services was added to NLRP3. Panel: Primary immunodeficiency disorders
Gene: nlrp3 has been classified as Green List (High Evidence).
Publications for NLRP3 were set to 11687797; 11992256; 12032915; 12522564; 28847925; 29366613
This gene has been classified as Green List (High Evidence).
Phenotypes for NLRP3 were set to CINCA syndrome 607115; Muckle-Wells syndrome 191900; Familial cold autoinflammatory syndrome 1 120100; Deafness, autosomal dominant 34, with or without inflammation 617772
Mode of inheritance for NLRP3 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for NLRP3 were set to CINCA syndrome; Muckle-Wells syndrome; Familial cold autoinflammatory syndrome
Expert Review Amber was added to NLRP3. Panel: Primary immunodeficiency disorders
ESID Registry 20171117 was added to NLRP3. Panel: Primary immunodeficiency disorders Phenotypes for gene NLRP3 were set to CINCA syndrome, Muckle-Wells syndrome, Muckle-Wells syndrome, Familial cold autoinflammatory syndrome
Phenotypes for gene NLRP3 were set to CINCA syndrome, Muckle-Wells syndrome, Muckle-Wells syndrome
NLRP3 was added to Primary immunodeficiency disorders panel. Sources: GRID V2.0
NLRP3 was created by Louise Daugherty