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Primary immunodeficiency

Gene: PRF1

Green List (high evidence)

PRF1 (perforin 1)
EnsemblGeneIds (GRCh38): ENSG00000180644
EnsemblGeneIds (GRCh37): ENSG00000180644
OMIM: 170280, Gene2Phenotype
PRF1 is in 7 panels

5 reviews

Eleanor Williams (Genomics England Curator)

Comment on list classification: Changed rating of gene from Red to Green. This gene was rated as Green in v2.208 and incorrectly automatically demoted to Red in v2.209. This was due to a defect in the automatic PanelApp uploading tool when a set of publications was added to the panel with the source ‘Other’, and under certain conditions associated to previous sources listed, resulted in the rating of the gene being automatically changed when it should not have been.
Created: 14 Oct 2020, 1:41 p.m. | Last Modified: 14 Oct 2020, 1:41 p.m.
Panel Version: 2.295
The following PubMed IDs were added to entity PRF1: 10583959;22248322;28468610;28806468. These publications have been associated with OMIM phenotype MIM#603553, which is listed for this entity, by the immunedysregulation subgroup of the Human Phenotype Ontology Immune Mediated Disorders Consortium (https://hpo-immune-mediated-disorders.groups.io/g/update) in August 2020.
Created: 13 Oct 2020, 9:36 a.m. | Last Modified: 13 Oct 2020, 9:36 a.m.
Panel Version: 2.208

Publications

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

Sophie Hambleton (Newcastle University)

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

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): PRF1 .PanelApp HGNC gene symbol check: PRF1 . IUIS Disease: Perforin deficiency (FHL2) . IUIS Inheritance: AR .T cells: Nl number, low nave T cells, restricted repertoire, poor proliferation to CD3, .B cells: Normal, .IUIS Other affected cells: N/A. IUIS Associated features: Fever, HSM, Hemophagocytic lymphohistiocytosis (HLH), cytopenias. IUIS Major category: Diseases of Immune Dysregulation. IUIS Subcategory: Familial Hemophagocytic Lymphohistiocytosis (FHL syndromes)
Created: 2 Jul 2018, 10:35 a.m.
from GeneReview PMID:20301617 20%-30% of Worldwide cases of FHL are FHL2 (PMID:15365097, PMID:15632205) and 50% in African American families 4 are FHL2 (PMID:14757862, PMID:16860143)
Created: 30 Apr 2018, 10:24 a.m.
Comment on publications: added genereview
Created: 30 Apr 2018, 10:17 a.m.
added early-onset tag
Created: 30 Apr 2018, 10:04 a.m.
Comment on list classification: Changed status from Amber to Green, there are more than 3 unrelated cases to support the phenotype Familial hemophagocytic lymphohistiocytosis-2 (FHL2) caused by homozygous or compound heterozygous mutation in the gene encoding perforin PRF1. Publications include: Goransdotter Ericson et al. (2001) PMID:11179007, where FHL2 was confirmed by genetic analysis reported 7 unrelated families. In PMID:10583959 Stepp et al. (1999) reported 8 unrelated patients with familial hemophagocytic lymphohistiocytosis linked to 10q21-q22, they sequenced the coding region of the PRF1 gene and identified homozygous nonsense mutations in 4 patients and missense mutations in the other 4 patients.
Created: 30 Apr 2018, 9:51 a.m.
Comment on publications: Added publications to support role of PRF1 variants in Hemophagocytic lymphohistiocytosis, familial, 2
Created: 30 Apr 2018, 9:43 a.m.
From OMIM: Familial hemophagocytic lymphohistiocytosis-2 (FHL2) is an autosomal recessive disorder of immune dysregulation with onset in infancy or early childhood. It is characterized clinically by fever, edema, hepatosplenomegaly, and liver dysfunction. Neurologic impairment, seizures, and ataxia are frequent. Laboratory studies show pancytopenia, coagulation abnormalities, hypofibrinogenemia, and hypertriglyceridemia.
Created: 30 Apr 2018, 9:41 a.m.
Comment on phenotypes: added synonyms
Created: 30 Apr 2018, 9:37 a.m.
Comment on phenotypes: added OMIM MIMid
Created: 30 Apr 2018, 9:35 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.
Original metadata downloaded from ESID Registry. ESID_Gene_original: PRF1, PanelApp HGNC gene symbol check: PRF1, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Diseases of immune dysregulation / Hemophagocytic Lymphohistiocytosis (HLH) / Familial hemophagocytic lymphohistiocytosis syndromes (FHLH)
Created: 17 Apr 2018, 12:29 p.m.
Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: PRF1, GRID_Gene_Symbol: PRF1, GRID_Transcript_ENS_Community submitted: ENST00000441259, GRID_Transcript_RefSeq: NM_001083116.1, GRID_Transcript_ENS_used_on_Production: ENST00000441259
Created: 17 Apr 2018, 12:12 p.m.

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Other
  • NHS GMS
  • North West GLH
  • London North GLH
  • IUIS Classification February 2018
  • Victorian Clinical Genetics Services
  • ESID Registry 20171117
  • GRID V2.0
  • GOSH PID v.8.0
Phenotypes
  • Hemophagocytic lymphohistiocytosis, familial 2, 603553
  • FHL2
  • Familial hemophagocytic lymphohistiocytosis syndromes (FHLH)
  • HPLH2
  • HLH2
  • Fever, HSM, Hemophagocytic lymphohistiocytosis (HLH), cytopenias
  • Diseases of Immune Dysregulation
Tags
early-onset
OMIM
170280
Clinvar variants
Variants in PRF1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

14 Oct 2020, Gel status: 3

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: prf1 has been classified as Green List (High Evidence).

13 Oct 2020, Gel status: 1

Added New Source, Set publications, Status Update

Eleanor Williams (Genomics England Curator)

Source Other was added to PRF1. Publications for gene PRF1 were updated from 11179007; 10583959; 12229880; 14757862; 20301617; 15365097; 15632205; 14757862; 16860143 to 28468610; 22248322; 12229880; 28806468; 15365097; 11179007; 14757862; 16860143; 10583959; 15632205; 20301617 Rating Changed from Green List (high evidence) to Red List (low evidence)

17 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to PRF1.

17 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source North West GLH was added to PRF1.

17 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source London North GLH was added to PRF1.

12 Jul 2018, Gel status: 4

Panel promoted to version 1.0

Louise Daugherty (Genomics England Curator)

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.

1 Jul 2018, Gel status: 4

Set penetrance

Louise Daugherty (Genomics England Curator)

Phenotypes for gene PRF1 were set to Hemophagocytic lymphohistiocytosis, familial 2, 603553, FHL2, Familial hemophagocytic lymphohistiocytosis syndromes (FHLH), HPLH2, HLH2, Fever, HSM, Hemophagocytic lymphohistiocytosis (HLH), cytopenias, Diseases of Immune Dysregulation

26 Jun 2018, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

IUIS Classification February 2018 was added to PRF1. Panel: Primary immunodeficiency disorders

26 Jun 2018, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

Victorian Clinical Genetics Services was added to PRF1. Panel: Primary immunodeficiency disorders

13 Jun 2018, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: prf1 has been classified as Green List (High Evidence).

30 Apr 2018, Gel status: 3

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for PRF1 were set to Hemophagocytic lymphohistiocytosis, familial 2, 603553; FHL2; Familial hemophagocytic lymphohistiocytosis syndromes (FHLH); HPLH2; HLH2

30 Apr 2018, Gel status: 3

Set publications

Louise Daugherty (Genomics England Curator)

Publications for PRF1 were set to 11179007; 10583959; 12229880; 14757862; 20301617; 15365097; 15632205; 14757862; 16860143

30 Apr 2018, Gel status: 3

Set publications

Louise Daugherty (Genomics England Curator)

Publications for PRF1 were set to 11179007; 10583959; 12229880; 14757862; 14757862; 20301617

30 Apr 2018, Gel status: 3

Gene classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

30 Apr 2018, Gel status: 2

Set publications

Louise Daugherty (Genomics England Curator)

Publications for PRF1 were set to 11179007; 10583959; 12229880; 14757862; 14757862

30 Apr 2018, Gel status: 2

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for PRF1 were set to Hemophagocytic lymphohistiocytosis, familial, 2, 603553; FHL2; Familial hemophagocytic lymphohistiocytosis syndromes (FHLH); HPLH2; HLH2

30 Apr 2018, Gel status: 2

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for PRF1 were set to Hemophagocytic lymphohistiocytosis, familial, 2, 603553; Familial hemophagocytic lymphohistiocytosis syndromes (FHLH)

20 Apr 2018, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

Expert Review Amber was added to PRF1. Panel: Primary immunodeficiency disorders

17 Apr 2018, Gel status: 1

Added New Source, Set penetrance

Louise Daugherty (Genomics England Curator)

ESID Registry 20171117 was added to PRF1. Panel: Primary immunodeficiency disorders Phenotypes for gene PRF1 were set to Hemophagocytic lymphohistiocytosis, familial, 2, Familial hemophagocytic lymphohistiocytosis syndromes (FHLH)

17 Apr 2018, Gel status: 1

Set penetrance

Louise Daugherty (Genomics England Curator)

Phenotypes for gene PRF1 were set to Hemophagocytic lymphohistiocytosis, familial, 2

17 Apr 2018, Gel status: 1

Added New Source, Set penetrance

Louise Daugherty (Genomics England Curator)

GRID V2.0 was added to PRF1. Panel: Primary immunodeficiency disorders Phenotypes for gene PRF1 were set to Hemophagocytic lymphohistiocytosis, familial, 2

6 Apr 2018, Gel status: 1

Clear Sources

Louise Daugherty (Genomics England Curator)

PRF1 Source: GOSH PID 20171180 was removed from gene: PRF1

6 Apr 2018, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

GOSH PID v.8.0 was added to PRF1. Panel: Primary immunodeficiency disorders

29 Mar 2018, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

PRF1 was added to Primary immunodeficiency disorders panel. Sources: GOSH PID 20171180

29 Mar 2018, Gel status: 1

Created

Louise Daugherty (Genomics England Curator)

PRF1 was created by Louise Daugherty