Genes in panel
STRs in panel
Prev Next

Primary immunodeficiency

Gene: RAC2

Amber List (moderate evidence)

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

9 reviews

Arina Puzriakova (Genomics England Curator)

Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag).
Created: 20 Oct 2020, 3:38 p.m. | Last Modified: 20 Oct 2020, 3:38 p.m.
Panel Version: 2.355

Ivone Leong (Genomics England Curator)

Comment on list classification: Promoted from Amber to Green based on expert review (Zornitza Stark) and evidence.
Created: 21 Apr 2020, 8:19 a.m. | Last Modified: 21 Apr 2020, 8:19 a.m.
Panel Version: 2.106

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Mono-allelic variants: GoF variants reported in at least 5 unrelated individuals, functional data including animal model.
Bi-allelic LoF variants associated with Neutrophil immunodeficiency syndrome, MIM# 608203; Common variable immunodeficiency
Created: 11 Apr 2020, 7:42 a.m. | Last Modified: 11 Apr 2020, 7:42 a.m.
Panel Version: 2.51

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
SCID; recurrent bacterial and viral infections; lymphoproliferation; neutropaenia; reticular dysgenesis; deafness; selective IgA deficiency; Reduced Ab responses following vaccination; Neutrophil immunodeficiency syndrome, MIM# 608203; Common variable immunodeficiency

Publications

Variants in this GENE are reported as part of current diagnostic practice

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
  • Expert Review Amber
  • IUIS Classification February 2018
  • Victorian Clinical Genetics Services
  • ESID Registry 20171117
  • GRID V2.0
  • SCID v1.6
  • Congenital neutropaenia v1.22
  • Combined B and T cell defect v1.12
Phenotypes
  • T-B- SCID
  • T-B+ SCID
  • Neutrophil immunodeficiency syndrome 608203
  • Neutrophil immunodeficiency syndrome
  • RAS-related C3 Bolutinum toxin substrate 2 deficiency (RAC2)
  • Poor wound healing, leukocytosis
  • Congenital defects of phagocyte number or function
  • Reticular dysgenesis
  • Recurrent sinopulmonary infections, selective IgA defiency
  • poststreptococcal glomerulonephritis
  • urticaria
Tags
watchlist for-review
OMIM
602049
Clinvar variants
Variants in RAC2
Penetrance
None
Publications
Panels with this gene

History Filter Activity

20 Oct 2020, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: rac2 has been classified as Amber List (Moderate Evidence).

20 Oct 2020, Gel status: 3

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag for-review tag was added to gene: RAC2.

21 Apr 2020, Gel status: 3

Entity classified by Genomics England curator

Ivone Leong (Genomics England Curator)

Gene: rac2 has been classified as Green List (High Evidence).

21 Apr 2020, Gel status: 2

Set publications

Ivone Leong (Genomics England Curator)

Publications for gene: RAC2 were set to 21167572; 30654050; 30723080; 31071452; 25512081; 10758162; 31382036; 10961859

28 Feb 2020, Gel status: 2

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene RAC2 were updated from 10961859; 10758162; 21167572; 25512081 to 21167572; 30654050; 30723080; 31071452; 25512081; 10758162; 31382036; 10961859

28 Feb 2020, Gel status: 2

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: RAC2 were changed from T-B- SCID; T-B+ SCID; Neutrophil immunodeficiency syndrome 608203; Neutrophil immunodeficiency syndrome; RAS-related C3 Bolutinum toxin substrate 2 deficiency (RAC2); Poor wound healing, leukocytosis; Congenital defects of phagocyte number or function to T-B- SCID; T-B+ SCID; Neutrophil immunodeficiency syndrome 608203; Neutrophil immunodeficiency syndrome; RAS-related C3 Bolutinum toxin substrate 2 deficiency (RAC2); Poor wound healing, leukocytosis; Congenital defects of phagocyte number or function; Reticular dysgenesis; Recurrent sinopulmonary infections, selective IgA defiency; poststreptococcal glomerulonephritis; urticaria

28 Feb 2020, Gel status: 2

Set mode of inheritance

Louise Daugherty (Genomics England Curator)

Mode of inheritance for gene: RAC2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

4 Oct 2018, Gel status: 2

Added Tag

Louise Daugherty (Genomics England Curator)

Tag watchlist tag was added to gene: RAC2.

12 Jul 2018, Gel status: 2

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.

11 Jul 2018, Gel status: 2

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: rac2 has been classified as Amber List (Moderate Evidence).

6 Jul 2018, Gel status: 2

Set mode of inheritance

Louise Daugherty (Genomics England Curator)

Mode of inheritance for gene: RAC2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

1 Jul 2018, Gel status: 2

Set penetrance

Louise Daugherty (Genomics England Curator)

Phenotypes for gene RAC2 were set to T-B- SCID, T-B+ SCID, Neutrophil immunodeficiency syndrome 608203, Neutrophil immunodeficiency syndrome, RAS-related C3 Bolutinum toxin substrate 2 deficiency (RAC2), Poor wound healing, leukocytosis, Congenital defects of phagocyte number or function

26 Jun 2018, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

IUIS Classification February 2018 was added to RAC2. Panel: Primary immunodeficiency disorders

26 Jun 2018, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

Victorian Clinical Genetics Services was added to RAC2. Panel: Primary immunodeficiency disorders

9 May 2018, Gel status: 2

Gene classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

This gene has been classified as Amber List (Moderate Evidence).

9 May 2018, Gel status: 2

Set publications

Sarah Leigh (Genomics England Curator)

Publications for RAC2 were set to 10961859; 10758162; 21167572; 25512081

9 May 2018, Gel status: 2

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for RAC2 were set to T-B- SCID; T-B+ SCID; Neutrophil immunodeficiency syndrome 608203; Neutrophil immunodeficiency syndrome; RAS-related C3 Bolutinum toxin substrate 2 deficiency (RAC2)

20 Apr 2018, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

Expert Review Amber was added to RAC2. 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 RAC2. Panel: Primary immunodeficiency disorders Phenotypes for gene RAC2 were set to T-B- SCID, T-B+ SCID, Neutrophil immunodeficiency syndrome, 608203, Neutrophil immunodeficiency syndrome, RAS-related C3 Bolutinum toxin substrate 2 deficiency (RAC2)

17 Apr 2018, Gel status: 1

Set penetrance

Louise Daugherty (Genomics England Curator)

Phenotypes for gene RAC2 were set to T-B- SCID, T-B+ SCID, Neutrophil immunodeficiency syndrome, 608203, Neutrophil immunodeficiency syndrome

17 Apr 2018, Gel status: 1

Added New Source, Set penetrance

Louise Daugherty (Genomics England Curator)

GRID V2.0 was added to RAC2. Panel: Primary immunodeficiency disorders Phenotypes for gene RAC2 were set to T-B- SCID, T-B+ SCID, Neutrophil immunodeficiency syndrome, 608203, Neutrophil immunodeficiency syndrome

29 Mar 2018, Gel status: 1

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for RAC2 were set to T-B- SCID; T-B+ SCID; Neutrophil immunodeficiency syndrome, 608203

29 Mar 2018, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

SCID v1.6 was added to RAC2. Panel: Primary immunodeficiency disorders

29 Mar 2018, Gel status: 1

Added New Source, Set mode of inheritance

Louise Daugherty (Genomics England Curator)

Congenital neutropaenia v1.22 was added to RAC2. Panel: Primary immunodeficiency disorders Model of inheritance for gene RAC2 was set to Unknown

29 Mar 2018, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

RAC2 was added to Primary immunodeficiency disorders panel. Sources: Expert Review Red, Combined B and T cell defect v1.12

29 Mar 2018, Gel status: 1

Created

Louise Daugherty (Genomics England Curator)

RAC2 was created by Louise Daugherty