Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: TCF3The 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, 10:35 a.m.
Panel Version: 2.529
Added 'for-review' tag as the MOI has changed since previous sign-off of this panel (version 2.1) and requires review by the Specialist Test Group.Created: 21 Oct 2020, 4:35 p.m. | Last Modified: 21 Oct 2020, 4:35 p.m.
Panel Version: 2.368
Comment on mode of inheritance: Updated MOI from Monoallelic to Both Monoallelic and biallelic based on expert review and evidence provided by Zornitza Stark (Australian Genomics).Created: 15 Apr 2020, 2:26 p.m. | Last Modified: 15 Apr 2020, 2:26 p.m.
Panel Version: 2.62
Please note recent reports of bi-allelic variants associated with disease.Created: 12 Apr 2020, 4:52 a.m. | Last Modified: 12 Apr 2020, 4:52 a.m.
Panel Version: 2.51
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications
agree with green geneCreated: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
YES- this is covered on our targeted exomeCreated: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
Comment on list classification: Sufficient number of cases for this gene to be rated green. Confirmed with Genomics England Clinical team.Created: 19 Jun 2018, 8:54 a.m.
Asked for Genomics England clinical team input to decide if this gene should be green. Enough cases but in some only mutations in the TCF3 were looked for.Created: 14 Jun 2018, 12:11 p.m.
As noted by Olivia Niblock, in the report from Boisson et al 2013 (PMID: 24216514), although 4 unrelated individuals with agammaglobulinemia (not from isolated populations or consanguineous families) all have a de novo missense mutation in the TCF3 gene (E555K) that appears to have a dominant negative effect, only 1 patient and their family underwent whole genome sequence analysis. One other patient is reported in Ben-Ali et al 2017 (PMID: 28532655) with severe hypogammaglobulinemia who was homozygous for a nonsense mutation p.Q270*. The first cousin parents were heterozygous for this variant. Ameratunga et al 2017 (PMID: 29114388) report a mother with a de novo TCF3 mutation in addition to an inherited C104R mutation of the TACI gene. The mother has severe CVID-like disorder and systemic lupus erythematosus (SLE). Her symptomatic son, who has inherited only the TCF3 mutation, but not the TACI gene mutation, has type 1 diabetes (T1D), synovitis, reduced IgG levels and IgA deficiency. In OMIM the TCF3 gene is associated with agammaglobulinemia. No data for this gene in gene2phenotype.Created: 13 Jun 2018, 1:27 p.m.
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): TCF3 .PanelApp HGNC gene symbol check: TCF3 . IUIS Disease: E47 transcription factor deficiency . IUIS Inheritance: AD .T cells: Nl numbers, low antigen specific memory CD4+, .B cells: N/A, .IUIS Other affected cells: N/A. IUIS Associated features: Recurrent bacterial infections. IUIS Major category: Predominantly Antibody Deficiencies. IUIS Subcategory: Severe Reduction in All Serum Immunoglobulin Isotypes with Profoundly Decreased or Absent B Cells, AgammaglobulinemiaCreated: 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, 10:28 a.m.
Original metadata downloaded from ESID Registry. ESID_Gene_original: TCF3, PanelApp HGNC gene symbol check: TCF3, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Predominantly antibody disorders / Agammaglobulinemias / AgammaglobulinemiaCreated: 17 Apr 2018, 12:29 p.m.
Comment on list classification: After literature research, while participants in a study in PMID: 24216514 all had the same variant, only one patient and their family had GWAS, highlighting variant in this gene. Another study in PMID 28532655 suggests a homozygous variant in an individual from a consanguineous family.Created: 15 Aug 2017, 12:54 p.m.
Four unrelated cases/families with same de novo missense variant (E555K). Suspected to be a dominant negative allele.Created: 16 May 2017, 7:56 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Agammaglobulinemia
Publications
Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Phenotypes for gene: TCF3 were changed from Agammaglobulinemia; Agammaglobulinemia 8, autosomal dominant, 616941; Primary immunodeficiency; Recurrent bacterial infections; Predominantly Antibody Deficiencies to Agammaglobulinemia 8A, autosomal dominant, OMIM:616941; Agammaglobulinemia 8B, autosomal recessive, OMIM:619824; Recurrent bacterial infections; Predominantly Antibody Deficiencies
Tag for-review was removed from gene: TCF3.
Tag for-review tag was added to gene: TCF3.
Mode of inheritance for gene: TCF3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TCF3 were set to 24216514; 28532655; 29114388
Source NHS GMS was added to TCF3.
Source North West GLH was added to TCF3.
Source London North GLH was added to TCF3.
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.
Phenotypes for gene TCF3 were set to Agammaglobulinemia, Agammaglobulinemia 8, autosomal dominant, 616941, Primary immunodeficiency, Recurrent bacterial infections, Predominantly Antibody Deficiencies
Gene: tcf3 has been classified as Green List (High Evidence).
IUIS Classification February 2018 was added to TCF3. Panel: Primary immunodeficiency disorders
Victorian Clinical Genetics Services was added to TCF3. Panel: Primary immunodeficiency disorders
Gene: tcf3 has been classified as Green List (High Evidence).
Publications for gene: TCF3 were set to 24216514; 28532655; 29114388
Phenotypes for TCF3 were set to Agammaglobulinemia; Agammaglobulinemia 8, autosomal dominant, 616941; Primary immunodeficiency
Phenotypes for TCF3 were set to Agammaglobulinemia; Agammaglobulinemia 8, autosomal dominant, 616941; Primary immunodeficiency
Mode of pathogenicity for TCF3 was changed to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
ESID Registry 20171117 was added to TCF3. Panel: Primary immunodeficiency disorders Phenotypes for gene TCF3 were set to Agammaglobulinemia
TCF3 was added to Primary immunodeficiency disorders panel. Sources: Expert Review Amber, A- or hypo-gammaglobulinaemia v1.25
TCF3 was created by Louise Daugherty