Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: FCGR3A

I don't know

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

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
predisposition to severe viral infection

I don't know

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 Hambleton

Created: 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 CD16

Created: 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 Infection

Created: 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 orphanet

Created: 18 Jun 2018, 3:20 p.m.

Comment on phenotypes: added OMIM MIMid

Created: 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 deficiencies

Created: 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: ENST00000367969

Created: 17 Apr 2018, 12:12 p.m.