Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: UNC13DComment 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, 4:46 p.m. | Last Modified: 14 Oct 2020, 4:46 p.m.
Panel Version: 2.331
The following PubMed IDs were added to entity UNC13D: 27914778;14622600;17993578;29312353. These publications have been associated with OMIM phenotype MIM#608898, which is listed for this entity, by the immunedysregulation 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): UNC13D .PanelApp HGNC gene symbol check: UNC13D . IUIS Disease: UNC13D / Munc13-4 deficiency (FHL3) . IUIS Inheritance: AR , .B cells: Normal, .IUIS Other affected cells: N/A. IUIS Associated features: Fever, HSM, HLH, cytopenias, . IUIS Major category: Diseases of Immune Dysregulation. IUIS Subcategory: Familial Hemophagocytic Lymphohistiocytosis (FHL syndromes)Created: 2 Jul 2018, 10:35 a.m.
Comment on list classification: Changed status from Amber to Green, there are more than 3 unrelated cases to support the phenotype Familial hemophagocytic lymphohistiocytosis-3 (FHL3) caused by homozygous or compound heterozygous mutation in the gene encoding perforin UNC13DCreated: 30 Apr 2018, 11:36 a.m.
from GeneReview PMID:20301617: Approx 20%-30% 3, 5 worldwide of FHL are FHL3 (Hemophagocytic lymphohistiocytosis, familial, 3) PMID:15632205, PMID:15703195.Created: 30 Apr 2018, 11:33 a.m.
Comment on publications: added publication PMID: 17993578 to support age-specific-variation tag eg: this gene is not specific to early onsetCreated: 30 Apr 2018, 11:30 a.m.
Added age-specific-variation tagCreated: 30 Apr 2018, 11:28 a.m.
from OMIM: Feldmann et al. (2003) PMID: 14622600 Identified 6 different mutations in the UNC13D gene in 10 patients from 7 unrelated families with Hemophagocytic lymphohistiocytosis-3 (FHL3). In a Turkish patient from a consanguineous family with primary hemophagocytic lymphohistiocytosis, Zur Stadt et al. (2006) PMID:16278825 identified homozygosity for a missense mutation in the UNC13D gene.
Rudd et al. (2008) PMID: 17993578 reported 9 patients from 6 families with genetically confirmed FHL3. There was considerable variation in age at diagnosis, ranging from birth to 14 years, and 3 of the 9 mutation-positive patients developed central nervous system symptoms. Natural killer cell activity was impaired in all 4 patients studied. Defective cytotoxic lymphocyte degranulation was evident in the 2 patients investigated, and was more pronounced in the patient with onset during infancy than in the patient with adolescent onset.Created: 30 Apr 2018, 11:26 a.m.
Comment on publications: Added publications to support role of UNC13D variants in Hemophagocytic lymphohistiocytosis, familial, 3Created: 30 Apr 2018, 11:22 a.m.
Comment on phenotypes: added OMIM MIMid and synonymsCreated: 30 Apr 2018, 11:17 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: 19 Apr 2018, 10:55 a.m.
Original metadata downloaded from ESID Registry. ESID_Gene_original: UNC13D, PanelApp HGNC gene symbol check: UNC13D, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Diseases of immune dysregulation / Hemophagocytic Lymphohistiocytosis (HLH) / Familial hemophagocytic lymphohistiocytosis syndromes (FHLH)Created: 17 Apr 2018, 12:29 p.m.
Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: UNC13D, GRID_Gene_Symbol: UNC13D, GRID_Transcript_ENS_Community submitted: ENST00000207549, GRID_Transcript_RefSeq: NM_199242.2, GRID_Transcript_ENS_used_on_Production: ENST00000207549Created: 17 Apr 2018, 12:12 p.m.
Gene: unc13d has been classified as Green List (High Evidence).
Source Other was added to UNC13D. Publications for gene UNC13D were updated from 14622600; 16278825; 15632205; 17993578; 15703195 to 15703195; 16278825; 17993578; 27914778; 15632205; 14622600; 29312353 Rating Changed from Green List (high evidence) to Red List (low evidence)
Source NHS GMS was added to UNC13D.
Source North West GLH was added to UNC13D.
Source London North GLH was added to UNC13D.
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 UNC13D were set to Hemophagocytic lymphohistiocytosis, familial 3, 608898, FHL3, Familial hemophagocytic lymphohistiocytosis syndromes (FHLH), HPLH3, HLH3, Fever, HSM, HLH, cytopenias,, Diseases of Immune Dysregulation
IUIS Classification February 2018 was added to UNC13D. Panel: Primary immunodeficiency disorders
Victorian Clinical Genetics Services was added to UNC13D. Panel: Primary immunodeficiency disorders
Gene: unc13d has been classified as Green List (High Evidence).
This gene has been classified as Green List (High Evidence).
Publications for UNC13D were set to 14622600; 16278825; 15632205; 17993578; 15703195
Publications for UNC13D were set to 14622600; 16278825; 15632205; 17993578
Publications for UNC13D were set to 14622600; 16278825; 15632205
Phenotypes for UNC13D were set to Hemophagocytic lymphohistiocytosis, familial 3, 608898; FHL3; Familial hemophagocytic lymphohistiocytosis syndromes (FHLH); HPLH3; HLH3
Phenotypes for UNC13D were set to Hemophagocytic lymphohistiocytosis, familial 3, 608898; FHL3; Familial hemophagocytic lymphohistiocytosis syndromes (FHLH); HPLH3; HLH3
This gene has been classified as Amber List (Moderate Evidence).
ESID Registry 20171117 was added to UNC13D. Panel: Primary immunodeficiency disorders Phenotypes for gene UNC13D were set to Hemophagocytic lymphohistiocytosis, familial, 3, Familial hemophagocytic lymphohistiocytosis syndromes (FHLH)
Phenotypes for gene UNC13D were set to Hemophagocytic lymphohistiocytosis, familial, 3
GRID V2.0 was added to UNC13D. Panel: Primary immunodeficiency disorders Model of inheritance for gene UNC13D was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene UNC13D were set to Hemophagocytic lymphohistiocytosis, familial, 3
UNC13D Source: GOSH PID 20171205 was removed from gene: UNC13D
GOSH PID v.8.0 was added to UNC13D. Panel: Primary immunodeficiency disorders
UNC13D was added to Primary immunodeficiency disorders panel. Sources: GOSH PID 20171205
UNC13D was created by Louise Daugherty