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COVID-19 research

Gene: TNFRSF13B

Green List (high evidence)

TNFRSF13B (TNF receptor superfamily member 13B)
EnsemblGeneIds (GRCh38): ENSG00000240505
EnsemblGeneIds (GRCh37): ENSG00000240505
OMIM: 604907, Gene2Phenotype
TNFRSF13B is in 5 panels

7 reviews

Zornitza Stark (Australian Genomics)

I don't know

Agree this gene is difficult to categorise. We have decided to include the gene in our panels, but report only the specific variants for which there is published evidence, and to report them as contributory rather than solely causative.
Created: 15 Jul 2018, 3:32 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

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

Eleanor Williams (Genomics England Curator)

Comment on list classification: Rated red following advice from the Genomics England clinical team. Further information is needed about this gene and its interactions.
Created: 5 Jul 2018, 8:59 p.m.
Comment on publications: Added publications relating to incomplete penetrance, gain of function and epistatic interactions with TCF3
Created: 3 Jul 2018, 12:26 p.m.
Consulting with the Genomics England Clinical team as to the appropriate colour rating of this gene.
Created: 3 Jul 2018, 12:22 p.m.
Although associated with Immunodeficiency, common variable, 2 and Immunoglobulin A deficiency 2 in OMIM and with Immunodeficiency, common variable, 2 in Gene2Phenotype and 6 variants reported in OMIM, there is some suggestion that variants in TNFRSF13B may not be solely causative. For example a study by Salzer et al 2009 (PMID:18981294) report on 7 familial cases of CVID where variants in TNFRSF13B were found, but also note that there are healthy or only mildly affected family members who have monoallelic or biallelic mutations, therefore mutations in TNFRSF13B are not 100% penetrant, and that two of the CVID patients have 2 wild-type TNFRSF13B alleles, hence mutations in TNFRSF13B/TACI are a contributing factor to develop CVID but are not solely causative.

A gain of function variant has also been reported by Peng et al 2017 (PMID: 28834165) in a family with two children with immune thrombocytopenia and a heterozygous G76S variant in TNFRSF13B. The healthy father was also heterozygous for this variant indicating incomplete penetrance.

Ameratunga et al 2017 (PMID: 29114388) report a family with a proband heterozygous for variants in both TNFRSF13B (C104R) and TCF3 (T168fsX191) and a severe CVID-like disorder while a sibling homozygous for the TNFRSF13B (C104R) only is in good health despite profound hypogammaglobulinemia and mild cytopenias and a son heterozygous for the TCF3 variant only has type 1 diabetes, arthritis, reduced IgG levels and IgA deficiency. Thus it appears that epistatic interactions between mutations of the TNFRSF13B/TACI and TCF3 signalling networks lead to the severe CVID-like disorder.
Created: 3 Jul 2018, 12:09 p.m.

Louise Daugherty (Genomics England Curator)

Red List (low evidence)

Additional external review this gene was reviewed again. Decided to keep Red on this panel, variants in this gene are contributory and not solely causative, more evidence is needed to understand the contribution to the disorder. We currently do not report contributory variants of a disorder, only causative.
Created: 21 Sep 2018, 10:15 a.m.
OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): TNFRSF13B (TACI) .PanelApp HGNC gene symbol check: TNFRSF13B . IUIS Disease: TACI deficiency . IUIS Inheritance: AD or AR .T cells: N/A, .B cells: N/A, .IUIS Other affected cells: N/A. IUIS Associated features: Variable clinical expression. IUIS Major category: Predominantly Antibody Deficiencies. IUIS Subcategory: Severe Reduction in at Least 2 Serum Immunoglobulin Isotypes with Normal or Low Number of B Cells, CVID Phenotype
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 Amber. 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, 10:27 a.m.
Original metadata downloaded from ESID Registry. ESID_Gene_original: TACI, PanelApp HGNC gene symbol check: TNFRSF13B, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Predominantly antibody disorders / Hypogammaglobulinemias / Common variable immunodeficiency disorders (CVID); Predominantly antibody disorders / Hypogammaglobulinemias / IgA with IgG subclass deficiency; Predominantly antibody disorders / Hypogammaglobulinemias / Isolated IgG subclass deficiency; Predominantly antibody disorders / Hypogammaglobulinemias / Selective IgA deficiency
Created: 17 Apr 2018, 12:29 p.m.
Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: TNFRSF13B, GRID_Gene_Symbol: TNFRSF13B, GRID_Transcript_ENS_Community submitted: ENST00000261652, GRID_Transcript_RefSeq: NM_012452.2, GRID_Transcript_ENS_used_on_Production: ENST00000261652
Created: 17 Apr 2018, 12:12 p.m.

William Rae (University Hospital Southampton NHS Foundation Trust)

Red List (low evidence)

Peter Arkwright (Royal Manchester Foundation Trust)

Red List (low evidence)

Sarah Leigh (Genomics England Curator)

Comment when marking as ready: Three negative expert reviews, 6 LOF variants reported in two publications. Association with Immunodeficiency, common variable, 2, 240500 in Gen2Phen
Created: 11 May 2016, 10:35 a.m.

Sophie Hambleton (Newcastle University)

Red List (low evidence)

Variants seem to behave as risk alleles and do not appear to act alone when disease occurs
Created: 19 Oct 2015, 2:37 p.m.

Mode of inheritance
Other

Phenotypes
CVID; IGAD

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
Phenotypes
  • IgA with IgG subclass deficiency
  • Immunodeficiency, common variable, 2
  • Immunodeficiency, common variable, 2, 240500
  • Variable clinical expression
  • Isolated IgG subclass deficiency
  • IGAD
  • Selective IgA deficiency
  • Common variable immunodeficiency disorders (CVID)
  • Predominantly Antibody Deficiencies
  • Immunoglobulin A deficiency 2, 609529
  • CVID
OMIM
604907
Clinvar variants
Variants in TNFRSF13B
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 TNFRSF13B. Added phenotypes IgA with IgG subclass deficiency; Immunodeficiency, common variable, 2; Immunodeficiency, common variable, 2, 240500; Variable clinical expression; Isolated IgG subclass deficiency; IGAD; Selective IgA deficiency; Common variable immunodeficiency disorders (CVID); Predominantly Antibody Deficiencies; Immunoglobulin A deficiency 2, 609529; CVID for gene: TNFRSF13B Rating Changed from Red List (low evidence) to Green List (high evidence)

1 Apr 2020, Gel status: 1

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

Ellen McDonagh (Genomics England Curator)

gene: TNFRSF13B was added gene: TNFRSF13B was added to Viral susceptibility. Sources: ESID Registry 20171117,Victorian Clinical Genetics Services,IUIS Classification December 2019,GRID V2.0,GOSH PID v.8.0,A- or hypo-gammaglobulinaemia v1.25,Expert Review Red,IUIS Classification February 2018 Mode of inheritance for gene: TNFRSF13B was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: TNFRSF13B were set to 29114388; 28834165; 16007086; 16007087; 32086639; 18981294; 32048120 Phenotypes for gene: TNFRSF13B were set to IgA with IgG subclass deficiency; Immunodeficiency, common variable, 2; Immunodeficiency, common variable, 2, 240500; Variable clinical expression; Isolated IgG subclass deficiency; IGAD; Selective IgA deficiency; Common variable immunodeficiency disorders (CVID); Predominantly Antibody Deficiencies; Immunoglobulin A deficiency 2, 609529; CVID