Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: RAC2The mode of inheritance of this gene has been approved by the NHS Genomic Medicine Service.Created: 4 Mar 2022, 10:17 a.m. | Last Modified: 4 Mar 2022, 10:36 a.m.
Panel Version: 2.529
The rating of this gene has been updated following NHS Genomic Medicine Service approval.Created: 4 Mar 2022, 10:17 a.m. | Last Modified: 4 Mar 2022, 10:17 a.m.
Panel Version: 2.529
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
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
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 immunodeficiencyCreated: 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
Added publication referenced by IUIS december 2019 updateCreated: 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 updateCreated: 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 MotilityCreated: 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 evidenceCreated: 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 evidenceCreated: 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 MotilityCreated: 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: ENST00000249071Created: 17 Apr 2018, 12:12 p.m.
Publications
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 sourcesCreated: 25 May 2016, 7:44 a.m.
Tag watchlist was removed from gene: RAC2. Tag for-review was removed from gene: RAC2.
Source Expert Review Green was added to RAC2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Gene: rac2 has been classified as Amber List (Moderate Evidence).
Tag for-review tag was added to gene: RAC2.
Gene: rac2 has been classified as Green List (High Evidence).
Publications for gene: RAC2 were set to 21167572; 30654050; 30723080; 31071452; 25512081; 10758162; 31382036; 10961859
Publications for gene RAC2 were updated from 10961859; 10758162; 21167572; 25512081 to 21167572; 30654050; 30723080; 31071452; 25512081; 10758162; 31382036; 10961859
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
Mode of inheritance for gene: RAC2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Tag watchlist tag was added to gene: RAC2.
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.
Gene: rac2 has been classified as Amber List (Moderate Evidence).
Mode of inheritance for gene: RAC2 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
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
IUIS Classification February 2018 was added to RAC2. Panel: Primary immunodeficiency disorders
Victorian Clinical Genetics Services was added to RAC2. Panel: Primary immunodeficiency disorders
This gene has been classified as Amber List (Moderate Evidence).
Publications for RAC2 were set to 10961859; 10758162; 21167572; 25512081
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)
Expert Review Amber was added to RAC2. Panel: Primary immunodeficiency disorders
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)
Phenotypes for gene RAC2 were set to T-B- SCID, T-B+ SCID, Neutrophil immunodeficiency syndrome, 608203, Neutrophil immunodeficiency syndrome
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
Phenotypes for RAC2 were set to T-B- SCID; T-B+ SCID; Neutrophil immunodeficiency syndrome, 608203
SCID v1.6 was added to RAC2. Panel: Primary immunodeficiency disorders
Congenital neutropaenia v1.22 was added to RAC2. Panel: Primary immunodeficiency disorders Model of inheritance for gene RAC2 was set to Unknown
RAC2 was added to Primary immunodeficiency disorders panel. Sources: Expert Review Red, Combined B and T cell defect v1.12
RAC2 was created by Louise Daugherty