Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: FCGR3A
Three patients reported in the literature homozygous for a specific variant in this gene p.(Leu66His) as noted in previous reviews; however, also note high population frequency, including homozygotes in ExAC.Created: 12 Jul 2018, 10:57 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Variants in this GENE are reported as part of current diagnostic practice
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
predisposition to severe viral infection
Additional external review added so this gene was reviewed again. Agree to keep this gene Amber until further evidence, noted there is a high population frequency, including homozygotes in ExAC but also Green review from Sophie HambletonCreated: 21 Sep 2018, 11:19 a.m.
Three cases, single variant identified to date. Rated amber for now and added watchlist tag. Will review again if further evidence to support Green rating by external expert.Created: 11 Jul 2018, 4:15 p.m.
Previous approved gene symbol CD16Created: 4 Jul 2018, 9:30 a.m.
OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): FCGR3A .PanelApp HGNC gene symbol check: FCGR3A . IUIS Disease: CD16 deficiency . IUIS Inheritance: AR .T cells: N/A, .B cells: N/A, .IUIS Other affected cells: NK cells. IUIS Associated features: severe herpes viral infections, particularly VZV, Epstein Barr virus (EBV), and (HPV). IUIS Major category: Defects in Intrinsic and Innate Immunity. IUIS Subcategory: Predisposition to Severe Viral InfectionCreated: 2 Jul 2018, 10:35 a.m.
Only a single variant reported in three unrelated cases with NK cells, not strong PID evidence. Keep Amber until more info on gene and disease association, refer to external expert review.Created: 18 Jun 2018, 4 p.m.
Comment on publications: added publications to support phenotype. A single variant has been reported in three unrelated cases. However it has been noted that high frequency of the variant NM_001127593.1:c.197T>A in the general population (5 homozygotes in ExAC), but homozygous change at this position has been reported in 3 individuals with NK cell deficiency. 2 probands had recurrent upper respiratory infections. In vitro study shows possible functional impact (PMID 23006327)Created: 18 Jun 2018, 3:45 p.m.
Results in defects in Intrinsic and Innate Immunity, clinical features include severe herpes viral infections particularly VZV, Epstein Barr virus (EBV), and (HPV)Created: 18 Jun 2018, 3:34 p.m.
Comment on phenotypes: added phenotype from orphanetCreated: 18 Jun 2018, 3:20 p.m.
Comment on phenotypes: added OMIM MIMidCreated: 18 Jun 2018, 3:19 p.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: FCGR3A, PanelApp HGNC gene symbol check: FCGR3A, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Other well defined PIDs / Fc receptor deficiencies / Fc receptor deficienciesCreated: 17 Apr 2018, 12:29 p.m.
Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: FCGR3A, GRID_Gene_Symbol: FCGR3A, GRID_Transcript_ENS_Community submitted: ENST00000367969, GRID_Transcript_RefSeq: NM_001127593.1, GRID_Transcript_ENS_used_on_Production: ENST00000367969Created: 17 Apr 2018, 12:12 p.m.
Source IUIS Classification December 2019 was added to FCGR3A. Added phenotypes severe herpes viral infections, particularly VZV, Epstein Barr virus (EBV), and (HPV) for gene: FCGR3A Publications for gene FCGR3A were updated from 8608639; 8874200; 23006327; 8609432 to 8874200; 23006327; 32048120; 8609432; 8608639; 32086639
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: fcgr3a has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: FCGR3A were set to Immunodeficiency 20, 615707; Fc receptor deficiencies; Autosomal recessive primary immunodeficiency with defective spontaneous NK cell cytotoxicity; CD16 deficiency; severe herpes viral infections, particularly VZV, Epstein Barr virus (EBV), and (HPV); Defects in Intrinsic and Innate Immunity; predisposition to severe viral infection
Phenotypes for gene FCGR3A were set to Immunodeficiency 20, 615707, Fc receptor deficiencies, Autosomal recessive primary immunodeficiency with defective spontaneous NK cell cytotoxicity, CD16 deficiency, severe herpes viral infections, particularly VZV, Epstein Barr virus (EBV), and (HPV), Defects in Intrinsic and Innate Immunity
IUIS Classification February 2018 was added to FCGR3A. Panel: Primary immunodeficiency disorders
Victorian Clinical Genetics Services was added to FCGR3A. Panel: Primary immunodeficiency disorders
Publications for gene: FCGR3A were set to 8608639; 8874200; 23006327; 8609432
Publications for gene: FCGR3A were set to 8608639; 8874200; 23006327
Phenotypes for gene: FCGR3A were set to Immunodeficiency 20, 615707; Fc receptor deficiencies; Autosomal recessive primary immunodeficiency with defective spontaneous NK cell cytotoxicity; CD16 deficiency
Phenotypes for gene: FCGR3A were set to Immunodeficiency 20, 615707; Fc receptor deficiencies; Autosomal recessive primary immunodeficiency with defective spontaneous NK cell cytotoxicity
Phenotypes for gene: FCGR3A were set to Immunodeficiency 20, 615707; Fc receptor deficiencies
Expert Review Amber was added to FCGR3A. Panel: Primary immunodeficiency disorders
ESID Registry 20171117 was added to FCGR3A. Panel: Primary immunodeficiency disorders Phenotypes for gene FCGR3A were set to Immunodeficiency 20, Fc receptor deficiencies
Phenotypes for gene FCGR3A were set to Immunodeficiency 20
FCGR3A was added to Primary immunodeficiency disorders panel. Sources: GRID V2.0
FCGR3A was created by Louise Daugherty