COVID-19 researchGene: FCN3
Probably not suitable for straightforward diagnostic reporting process
Created: 29 Jun 2018, 2:08 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Zornitza Stark (VCGS) , pers. comm. notes there are multiple cases reported, but single variant, and rates the gene Green. However, as highlighted by previous expert review it is not suitable for straightforward diagnostic reporting process, further evidence is needed since the consequences of FCN3 deficiency do not seem to be not clear-cut, and it has been suggested that it may act as a disease modifier.
Created: 21 Sep 2018, 12:20 p.m.
Comment on list classification: Changed from Amber to Red due to Red review from external expert, agreeing this gene for straightforward diagnostic reporting process. To be referred back to Victorian Clinical Genetics Services for evidences.
Created: 4 Jul 2018, 10:01 a.m.
OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): FCN3 .PanelApp HGNC gene symbol check: FCN3 . IUIS Disease: Ficolin 3 deficiency . IUIS Inheritance: AR .T cells: N/A, .B cells: N/A, .IUIS Other affected cells: N/A. IUIS Associated features: Respiratory infections, abscesses. IUIS Major category: Complement Deficiencies. IUIS Subcategory: N/A
Created: 2 Jul 2018, 10:35 a.m.
Keep Amber until more info on gene and disease association, refer to external expert review. Only one variant reported to date, Michalski et al. (2012) PMID: 22226667 concluded that heterozygosity for the FCN3 variant does not seem to have major clinical importance PMID: 25662573, then in 2015 Michalski et al. PMID: 25662573 concluded that the consequences of FCN3 deficiency are not clear-cut, and suggested that it may act as a disease modifier.
Created: 19 Jun 2018, 10:46 a.m.
from PMID: 25662573, 19535802, Orphanet Immunodeficiency due to ficolin3 deficiency is a rare, genetic, immunodeficiency due to a complement cascade protein anomaly characterized by low or undetectable serum ficolin3 levels, susceptibility to infections, and possibly autoimmunity. The presentation is variable, from perinatal necrotizing enterocolitis and recurrent skin infections with Staphylococcus aureus to childhood-onset recurrent pulmonary infections leading to brain abscesses and pulmonary fibrosis, to membranous nephropathy. In some patients, clinical consequences of ficolin3 deficiency were not clear.
Created: 19 Jun 2018, 10:39 a.m.
Comment on publications: added publications to support the phenotype
Created: 19 Jun 2018, 10:39 a.m.
Comment on mode of inheritance: added MOI from PMID: 20971976
Created: 19 Jun 2018, 10:36 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: FCN3, PanelApp HGNC gene symbol check: FCN3, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Complement deficiencies / Complement deficiency / Ficolin3 deficiency
Created: 17 Apr 2018, 12:29 p.m.
Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: FCN3, GRID_Gene_Symbol: FCN3, GRID_Transcript_ENS_Community submitted: ENST00000270879, GRID_Transcript_RefSeq: NM_003665.2, GRID_Transcript_ENS_used_on_Production: ENST00000270879
Created: 17 Apr 2018, 12:12 p.m.
Source Expert Review Green was added to FCN3. Added phenotypes Respiratory infections, abscesses; Complement Deficiencies; Ficolin3 deficiency; Immunodeficiency due to ficolin 3 deficiency, 613860 for gene: FCN3 Rating Changed from Red List (low evidence) to Green List (high evidence)
gene: FCN3 was added gene: FCN3 was added to Viral susceptibility. Sources: ESID Registry 20171117,Victorian Clinical Genetics Services,GRID V2.0,IUIS Classification December 2019,Expert Review Red,IUIS Classification February 2018 Mode of inheritance for gene: FCN3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FCN3 were set to 25662573; 19535802; 32086639; 32048120; 20971976; 22226667 Phenotypes for gene: FCN3 were set to Respiratory infections, abscesses; Complement Deficiencies; Ficolin3 deficiency; Immunodeficiency due to ficolin 3 deficiency, 613860