Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: CFHR5The rating of this gene has been updated from Amber to Red following NHS Genomic Medicine Service approval.Created: 29 Jul 2022, 1:47 p.m. | Last Modified: 29 Jul 2022, 1:47 p.m.
Panel Version: 2.572
Not enough evidence for monogenic PIDCreated: 20 Jun 2022, 10:42 a.m. | Last Modified: 20 Jun 2022, 10:42 a.m.
Panel Version: 2.555
agree with all the Amber genesCreated: 25 Sep 2019, 1:49 p.m. | Last Modified: 25 Sep 2019, 1:49 p.m.
Panel Version: 1.115
The amber genes are covered on our targeted exome, we feel that these should be covered in the testingCreated: 25 Sep 2019, 1:44 p.m. | Last Modified: 25 Sep 2019, 1:44 p.m.
Panel Version: 1.114
agreeCreated: 29 Jun 2018, 1:35 p.m.
Glomerulonephritis with C3 deposits (green re association - ?phenotype)Created: 26 Sep 2019, 3:51 p.m. | Last Modified: 26 Sep 2019, 3:51 p.m.
Panel Version: 1.130
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 only enough evidence to rate this gene Amber.Created: 25 Sep 2019, 3 p.m. | Last Modified: 25 Sep 2019, 3 p.m.
Panel Version: 1.116
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 only enough evidence to rate this gene AmberCreated: 25 Sep 2019, 3 p.m. | Last Modified: 25 Sep 2019, 3 p.m.
Panel Version: 1.116
Comment on mode of inheritance: Changed MOI in view of IUIS dataCreated: 29 Mar 2019, 3:07 p.m.
After internal and external review, it was agreed this gene should remain Amber (it is listed on the GRID and VCGS panel)Created: 3 Jul 2018, 9:24 a.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: CFHR5 . IUIS Disease: Factor H -related protein deficiencies . IUIS Inheritance: AR or AD .T cells: N/A, .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/ACreated: 2 Jul 2018, 10:35 a.m.
After internal clinical review it was agreed that the phenotype is better suited to a panel to cover the new disease: Familial IgA nephropathy and IgA vasculitis. Although this panel includes complement deficiencies, CFHR5 sequence variants seem to be risk factors/'susceptibility factors for the development of chronic kidney disease after streptococcal infection / Familial IgA nephropathy and IgA vasculitis. Also only be one cnv (not published but in Clinvar) https://www.ncbi.nlm.nih.gov/clinvar?term=608593[MIM] , remainder are duplication/fusion/rearrangement events.Created: 8 Jun 2018, 3:30 p.m.
For internal clinical review- Not sure if CFHR5 sequence variants that are risk factors for the development of chronic kidney disease after streptococcal infection is applicable to this panelCreated: 8 Jun 2018, 12:46 p.m.
The commonest cause of Nephropathy due to CFHR5 deficiency is complement factor H-related 5 (CFHR5), which is endemic in Greek Cypriots. Genetic evidence implicates some of the same complement regulators in the aetiology of common immune complex glomerular disorders such as IgA nephropathy and lupus nephritis. Complement is an important aspect of defence against infection
Created: 8 Jun 2018, 11:57 a.m.
Comment on phenotypes: added phenotype from orphanetCreated: 7 Jun 2018, 4:27 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 supplied by GRID. GRID Gene Symbol HGNC PanelApp check: CFHR5, GRID_Gene_Symbol: CFHR5, GRID_Transcript_ENS_Community submitted: ENST00000256785, GRID_Transcript_RefSeq: NM_030787.3, GRID_Transcript_ENS_used_on_Production: ENST00000256785Created: 17 Apr 2018, 12:12 p.m.
Source Expert Review Red was added to CFHR5. Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Source IUIS Classification December 2019 was added to CFHR5. Added phenotypes Older onset atypical hemolytic-uremic syndrome, disseminated neisserial infections for gene: CFHR5 Publications for gene CFHR5 were updated from 20800271; 22503529; 28673452 to 32048120; 28673452; 20800271; 22503529; 32086639
Source North West GLH was added to CFHR5.
Source London North GLH was added to CFHR5.
Source NHS GMS was added to CFHR5.
Mode of inheritance for gene: CFHR5 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
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 CFHR5 were set to Nephropathy due to CFHR5 deficiency, 614809, Atypical hemolytic uremic syndrome susceptibility, Atypical hemolytic-uremic syndrome with anti-factor H antibodies, Older onset atypical hemolytic-uremic syndrome, disseminated neisserial infections, Complement Deficiencies
Gene: cfhr5 has been classified as Amber List (Moderate Evidence).
IUIS Classification February 2018 was added to CFHR5. Panel: Primary immunodeficiency disorders
Victorian Clinical Genetics Services was added to CFHR5. Panel: Primary immunodeficiency disorders
Publications for gene: CFHR5 were set to 20800271; 22503529; 28673452
Phenotypes for gene: CFHR5 were set to Nephropathy due to CFHR5 deficiency, 614809; Atypical hemolytic uremic syndrome susceptibility; Atypical hemolytic-uremic syndrome with anti-factor H antibodies
Phenotypes for gene: CFHR5 were set to Nephropathy due to CFHR5 deficiency, 614809Atypical hemolytic uremic syndrome susceptibility; Atypical hemolytic-uremic syndrome with anti-factor H antibodies
Phenotypes for gene: CFHR5 were set to Nephropathy due to CFHR5 deficiency; Atypical hemolytic uremic syndrome susceptibility; Atypical hemolytic-uremic syndrome with anti-factor H antibodies
Expert Review Amber was added to CFHR5. Panel: Primary immunodeficiency disorders
Phenotypes for gene CFHR5 were set to Nephropathy due to CFHR5 deficiency, Atypical hemolytic uremic syndrome susceptibility
CFHR5 was added to Primary immunodeficiency disorders panel. Sources: GRID V2.0
CFHR5 was created by Louise Daugherty