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STRs in panel
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COVID-19 research

Gene: PLCG2

Green List (high evidence)

PLCG2 (phospholipase C gamma 2)
EnsemblGeneIds (GRCh38): ENSG00000197943
EnsemblGeneIds (GRCh37): ENSG00000197943
OMIM: 600220, Gene2Phenotype
PLCG2 is in 6 panels

8 reviews

Kimberly Gilmour (Great Ormond Street Hopsital)

Green List (high evidence)

agree with green gene
Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94

Tracy Briggs (Manchester Genomic Medicine Centre)

Green List (high evidence)

YES- this is covered on our targeted exome
Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94

Sarah Leigh (Genomics England Curator)

Comment on list classification: Associated with relevant phenotypes in OMIM and as possible Gen2Phen gene. At least 3 large inframe deletion variants have been reported in unrelated Familial cold autoinflammatory syndrome 3 614468 cases. These deletions remove, the C-terminal Src-homology-2 (cSH2) domain, which is autoinhibitory and normally prevents constitutive enzymatic function, hence the deletions are gain of function (PMID 22236196). The missense variant (NM_002661, c.2120C>A, p.Ser707Tyr) also falls within the cSH2 domain, it does not result in loss of inhibition alone, but requires other stimulating factors also (PMID 23000145)
Created: 9 May 2018, 11:55 a.m.

Louise Daugherty (Genomics England Curator)

Green List (high evidence)

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): PLCG2 .PanelApp HGNC gene symbol check: PLCG2 . IUIS Disease: PLAID (PLCg2 associated antibody deficiency and immune dysregulation) or familial cold autoinflammatory syndrome 3 or APLAID (c2120A>C) . IUIS Inheritance: AD GOF .T cells: Very low, .B cells: N/A, .IUIS Other affected cells: B cells, NK, Mast cells. IUIS Associated features: Cold urticaria hypogammaglobulinemia, autoinflammation. IUIS Major category: Autoinflammatory Disorders. IUIS Subcategory: Defects Affecting the Inflammasome
Created: 2 Jul 2018, 10:35 a.m.
This gene was present in the original PanelApp PID panel dataset (review in April 2018) rated as Amber. The gene is present in the 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, 10:29 a.m.
Original metadata downloaded from ESID Registry. ESID_Gene_original: PLCG2, PanelApp HGNC gene symbol check: PLCG2, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Autoinflammatory disorders / Other autoinflammatory diseases with known genetic defect / Other autoinflammatory diseases with known genetic defect
Created: 17 Apr 2018, 12:29 p.m.
Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: PLCG2, GRID_Gene_Symbol: PLCG2, GRID_Transcript_ENS_Community submitted: ENST00000359376, GRID_Transcript_RefSeq: NM_002661.4, GRID_Transcript_ENS_used_on_Production: ENST00000359376
Created: 17 Apr 2018, 12:12 p.m.

Olivia Niblock (Genomics England Curator)

Comment on list classification: Variants in this gene are certainly linked to immunodeficiency. From literature review, found 2 papers documenting variation in this gene being linked to hypo-gammaglobulinaemia, the first paper 22236196, citing 3 individuals being treated for hypo-gammaglobulinaemia, however not clear if these individuals are related.
Created: 15 Aug 2017, 1:17 p.m.
Comment on mode of pathogenicity: Gain of Function
Created: 15 Aug 2017, 1:09 p.m.

Sophie Hambleton (Newcastle University)

Green List (high evidence)

Disease alleles cause gain of phospholipase activity that may or may not be temperature-dependent
Created: 6 Jan 2017, 3:30 p.m.

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

Ellen McDonagh (Genomics England Curator)

It is a possible DD gene for Autoinflammation, antibody deficiency, and immune dysregulation syndrome-PLCG2 associated, and a possible DD gene for Familial cold autoinflammatory syndrome 3.
Created: 9 Sep 2016, 8:29 a.m.

William Rae (University Hospital Southampton NHS Foundation Trust)

Green List (high evidence)

Gain of function variants.
Created: 6 Sep 2016, 5:20 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Hypogammaglobulinaemia, cold induced urticaria, autoinflammatory

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
Phenotypes
  • Other autoinflammatory diseases with known genetic defect
  • Cold urticaria hypogammaglobulinemia, autoinflammation
  • Familial cold autoinflammatory syndrome 3 614468
  • Familial cold autoinflammatory syndrome 3
  • Autoinflammatory Disorders
  • Hypogammaglobulinaemia, cold induced urticaria, autoinflammatory
  • Autoinflammation, antibody deficiency, and immune dysregulation syndrome 614878
OMIM
600220
Clinvar variants
Variants in PLCG2
Penetrance
None
Publications
Mode of Pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Panels with this gene

History Filter Activity

1 Apr 2020, Gel status: 3

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes, Set mode of pathogenicity

Ellen McDonagh (Genomics England Curator)

gene: PLCG2 was added gene: PLCG2 was added to Viral susceptibility. Sources: Expert Review Green,ESID Registry 20171117,North West GLH,Victorian Clinical Genetics Services,GRID V2.0,NHS GMS,GOSH PID v.8.0,London North GLH,A- or hypo-gammaglobulinaemia v1.25,IUIS Classification February 2018 Mode of inheritance for gene: PLCG2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: PLCG2 were set to 29538758; 23000145; 22236196 Phenotypes for gene: PLCG2 were set to Other autoinflammatory diseases with known genetic defect; Cold urticaria hypogammaglobulinemia, autoinflammation; Familial cold autoinflammatory syndrome 3 614468; Familial cold autoinflammatory syndrome 3; Autoinflammatory Disorders; Hypogammaglobulinaemia, cold induced urticaria, autoinflammatory; Autoinflammation, antibody deficiency, and immune dysregulation syndrome 614878 Mode of pathogenicity for gene: PLCG2 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments