Primary immunodeficiencyGene: CFHR2
Genetically complex, not Mendelian
Created: 11 Jun 2018, 4:21 p.m.
OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): CFHR1-5 .PanelApp HGNC gene symbol check: CFHR2 . IUIS Disease: Factor H -related protein deficiencies . IUIS Inheritance: AR or AD .T cells: Nl to low, poor proliferation to antigen, .B cells: N/A, .IUIS Other affected cells: N/A. IUIS Associated features: Older onset atypical hemolytic-uremic syndrome, disseminated neisserial infections. IUIS Major category: Complement Deficiencies. IUIS Subcategory: N/A
Created: 2 Jul 2018, 10:35 a.m.
External expert review notes Amber status, but as it is not Mendelian disorder I have kept this gene Red on this panel until further evidence to support upgrading the status
Created: 12 Jun 2018, 12:25 p.m.
Comment on list classification: Changed from Amber to Red. This gene was only found in the v2.0 GRID dataset, but there is no current evidence in the literature to support the pertinence of this gene and immunity yet. GRID team confirm this gene will be removed/downgraded from Tier1 in their next iteration of the GRID panel- so agree it should be Red and not Amber
Created: 26 Apr 2018, 8:39 a.m.
Although CFHR2 is part of the complement system there is not enough evidence currently to support variants of this gene being linked to a immunity disorder. In addition to this, GRID will be removing CFHR2 as a Tier 1 gene from their panel after clincial input that there is no known pertinent PID disorder linked to this gene yet (pers comm Karyn Megy)
Created: 26 Apr 2018, 8:35 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.
Pers. comm with Karyn Megy, WGS Clinical Feedback Lead that this gene is not pertinent, and will be removed from the GRID panel
Created: 19 Apr 2018, 8:54 a.m.
Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: CFHR2, GRID_Gene_Symbol: CFHR2, GRID_Transcript_ENS_Community submitted: ENST00000367415, GRID_Transcript_RefSeq: NM_005666.3, GRID_Transcript_ENS_used_on_Production: ENST00000367415
Created: 17 Apr 2018, 12:12 p.m.
Source IUIS Classification December 2019 was added to CFHR2. Mode of inheritance for gene CFHR2 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Added phenotypes Older onset atypical hemolytic-uremic syndrome, disseminated neisserial infections for gene: CFHR2 Publications for gene CFHR2 were updated from to 32048120; 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.
Phenotypes for gene CFHR2 were set to Age related macular degeneration, Atypical hemolytic uremic syndrome susceptibility, Older onset atypical hemolytic-uremic syndrome, disseminated neisserial infections, Complement Deficiencies
IUIS Classification February 2018 was added to CFHR2. Panel: Primary immunodeficiency disorders
Victorian Clinical Genetics Services was added to CFHR2. Panel: Primary immunodeficiency disorders
Gene: cfhr2 has been classified as Red List (Low Evidence).
This gene has been classified as Red List (Low Evidence).
Phenotypes for CFHR2 were set to Age related macular degeneration; Atypical hemolytic uremic syndrome susceptibility
Expert Review Amber was added to CFHR2. Panel: Primary immunodeficiency disorders
Phenotypes for gene CFHR2 were set to Age related macular degeneration, Atypical hemolytic uremic syndrome susceptibility, Atypical hemolytic uremic syndrome susceptibility
CFHR2 was added to Primary immunodeficiency disorders panel. Sources: GRID V2.0
CFHR2 was created by Louise Daugherty