Genes in panel
STRs in panel
Prev Next

COVID-19 research

Gene: RAC2

Green List (high evidence)

RAC2 (Rac family small GTPase 2)
EnsemblGeneIds (GRCh38): ENSG00000128340
EnsemblGeneIds (GRCh37): ENSG00000128340
OMIM: 602049, Gene2Phenotype
RAC2 is in 5 panels

6 reviews

Louise Daugherty (Genomics England Curator)

I don't know

Added publication referenced by IUIS december 2019 update
Created: 28 Feb 2020, 8:49 p.m. | Last Modified: 28 Feb 2020, 8:49 p.m.
Panel Version: 2.36
Comment on mode of inheritance: changed MOI due to IUIS December 2019 update
Created: 28 Feb 2020, 4:46 p.m. | Last Modified: 28 Feb 2020, 4:46 p.m.
Panel Version: 2.28
Original Metadata from IUIS classification table (December, 2019). IUIS Genetic defect (original gene symbol in IUIS download): RAC2 .PanelApp HGNC gene symbol check: RAC2 . IUIS Disease: RAC2 deficiency . IUIS Inheritance: AD GOF / AR / AD LOF, T cells: Very low / no data, .B cells: Very low / no data, Immunoglobulin levels: Low / low, Neutrophil count: Low / High.IUIS Other affected cells: N. IUIS Associated features: Reticular dysgenesis / Recurrent sinopulmonary infections, selective IgA defiency; poststreptococcal glomerulonephritis; urticaria Poor wound healing, leukocytosis, IUIS Major category: TImmunodeficiencies affecting cellular and humoral immunity / Predominantly Antibody Deficiencies / Congenital defects of phagocyte number or function. IUIS Subcategory: T-B- SCID / CVID Phenotype/ Defects of Motility
Created: 28 Feb 2020, 4:45 p.m. | Last Modified: 28 Feb 2020, 4:45 p.m.
Panel Version: 2.27
Added watch list tag. Decided to leave the rating for this gene as Amber, this is borderline, as the Invitae reported variant would make a second case, but there is not enough supporting evidence
Created: 4 Oct 2018, 2:57 p.m.
Zornitza Stark (VCGS) , pers. comm. notes 2 families/functional evidence.
There is only a single variant reported and confirmed in the literature NM_002872.4(RAC2):c.169G>A (p.Asp57Asn) that results in Neutrophil immunodeficiency syndrome PMID: 10758162. There is a second variant reported in clinvar by a Invitae NM_002872.4(RAC2):c.184G>A (p.Glu62Lys), the supporting information denotes "This variant is not present in population databases (ExAC no frequency) and has been shown to arise de novo in an individual affected with severe combined immunodeficiency (Invitae)".
Created: 21 Sep 2018, 12:45 p.m.
PMID: 10961859 reported functional studies demonstrating that the D57N mutant behaves in a dominant-negative fashion at the cellular level.
Created: 21 Sep 2018, 12:29 p.m.
Amber rating. Current literature indicates 1 variants in 3 unrelated families. In OMIM of a relevant phenotype (severe bacterial infections in infancy) is reported. Red ratings highly likely to be historical ratings made prior to further evidence
Created: 11 Jul 2018, 4:01 p.m.
OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): RAC2 .PanelApp HGNC gene symbol check: RAC2 . IUIS Disease: RAC2 deficiency . IUIS Inheritance: AD .T cells: Decreased, .B cells: N/A, .IUIS Other affected cells: N. IUIS Associated features: Poor wound healing, leukocytosis. IUIS Major category: Congenital defects of phagocyte number or function. IUIS Subcategory: Defects of Motility
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 Red. 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, 12:25 p.m.
Original metadata downloaded from ESID Registry. ESID_Gene_original: RAC2, PanelApp HGNC gene symbol check: RAC2, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Phagocytic disorders / RAC2-GTPase defect / RAS-related C3 Bolutinum toxin substrate 2 deficiency (RAC2)
Created: 17 Apr 2018, 12:29 p.m.
Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: RAC2, GRID_Gene_Symbol: RAC2, GRID_Transcript_ENS_Community submitted: ENST00000249071, GRID_Transcript_RefSeq: NM_002872.3, GRID_Transcript_ENS_used_on_Production: ENST00000249071
Created: 17 Apr 2018, 12:12 p.m.

Publications

Sophie Hambleton (Newcastle University)

Red List (low evidence)

Tracy Briggs (Manchester Genomic Medicine Centre)

Red List (low evidence)

Peter Arkwright (Royal Manchester Foundation Trust)

Red List (low evidence)

Kimberly Gilmour (Great Ormond Street Hopsital)

Red List (low evidence)

Sarah Leigh (Genomics England Curator)

Comment on list classification: Associated with phenotype in OMIM and not in Gen2Phen. At least 2 variants identified in 3 unrelated cases.
Created: 9 May 2018, 2:34 p.m.
Comment when marking as ready: Associated with Neutrophil immunodeficiency syndrome, 608203 in OMIM, no disease association in G2P. Expert review red and 1/4 sources
Created: 25 May 2016, 7:44 a.m.

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
Phenotypes
  • Reticular dysgenesis
  • poststreptococcal glomerulonephritis
  • Congenital defects of phagocyte number or function
  • Neutrophil immunodeficiency syndrome
  • RAS-related C3 Bolutinum toxin substrate 2 deficiency (RAC2)
  • T-B+ SCID
  • Neutrophil immunodeficiency syndrome 608203
  • Recurrent sinopulmonary infections, selective IgA defiency
  • urticaria
  • T-B- SCID
  • Poor wound healing, leukocytosis
OMIM
602049
Clinvar variants
Variants in RAC2
Penetrance
None
Publications
Panels with this gene

History Filter Activity

2 Apr 2020, Gel status: 3

Added New Source, Set Phenotypes, Status Update

Ellen McDonagh (Genomics England Curator)

Source Expert Review Green was added to RAC2. Added phenotypes Reticular dysgenesis; poststreptococcal glomerulonephritis; Congenital defects of phagocyte number or function; Neutrophil immunodeficiency syndrome; RAS-related C3 Bolutinum toxin substrate 2 deficiency (RAC2); T-B+ SCID; Neutrophil immunodeficiency syndrome 608203; Recurrent sinopulmonary infections, selective IgA defiency; urticaria; T-B- SCID; Poor wound healing, leukocytosis for gene: RAC2 Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

1 Apr 2020, Gel status: 2

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

Ellen McDonagh (Genomics England Curator)

gene: RAC2 was added gene: RAC2 was added to Viral susceptibility. Sources: Combined B and T cell defect v1.12,ESID Registry 20171117,Victorian Clinical Genetics Services,Congenital neutropaenia v1.22,GRID V2.0,SCID v1.6,IUIS Classification February 2018,Expert Review Amber Mode of inheritance for gene: RAC2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: RAC2 were set to 21167572; 30654050; 30723080; 31071452; 25512081; 10758162; 31382036; 10961859 Phenotypes for gene: RAC2 were set to Reticular dysgenesis; poststreptococcal glomerulonephritis; Congenital defects of phagocyte number or function; Neutrophil immunodeficiency syndrome; RAS-related C3 Bolutinum toxin substrate 2 deficiency (RAC2); T-B+ SCID; Neutrophil immunodeficiency syndrome 608203; Recurrent sinopulmonary infections, selective IgA defiency; urticaria; T-B- SCID; Poor wound healing, leukocytosis