Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: TCN2

Comment on list classification: Changed rating of gene from Red to Green. This gene was rated as Green in v2.208 and incorrectly automatically demoted to Red in v2.209. This was due to a defect in the automatic PanelApp uploading tool when a set of publications was added to the panel with the source ‘Other’, and under certain conditions associated to previous sources listed, resulted in the rating of the gene being automatically changed when it should not have been.

Created: 14 Oct 2020, 4:41 p.m. | Last Modified: 14 Oct 2020, 4:41 p.m.

Panel Version: 2.323

The following PubMed IDs were added to gene TCN2 (OMIM gene MIM#613441): 7849710;19373259;12107818. These publications have been associated with the gene by the immunodeficiencies subgroup of the Human Phenotype Ontology Immune Mediated Disorders Consortium (https://hpo-immune-mediated-disorders.groups.io/g/update) in August 2020.

Created: 13 Oct 2020, 9:36 a.m. | Last Modified: 13 Oct 2020, 9:36 a.m.

Panel Version: 2.208

Publications

• 7849710
• 19373259
• 12107818

Green List (high evidence)

agree with green gene

Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.

Panel Version: 1.94

Green List (high evidence)

YES- this is covered on our targeted exome

Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.

Panel Version: 1.94

Green List (high evidence)

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): TCN2 .PanelApp HGNC gene symbol check: TCN2 . IUIS Disease: Transcobalamin 2 deficiency . IUIS Inheritance: AR .T cells: N/A, .B cells: Variable, .IUIS Other affected cells: N/A. IUIS Associated features: Megaloblastic anemia, pancytopenia, if untreated for prolonged periods results in intellectual disability. IUIS Major category: Combined immunodeficiencies with associated or syndromic features. IUIS Subcategory: Defects of Vitamin B12 and Folate Metabolism

Created: 2 Jul 2018, 10:35 a.m.

Original metadata downloaded from ESID Registry. ESID_Gene_original: TCN2, PanelApp HGNC gene symbol check: TCN2, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Other well defined PIDs / Defects of Vitamin B12 and Folate metabolism / Defects of Vitamin B12 and Folate metabolism; Predominantly antibody disorders / Hypogammaglobulinemias / Transcobalamin II deficiency

Created: 17 Apr 2018, 12:29 p.m.

Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: TCN2, GRID_Gene_Symbol: TCN2, GRID_Transcript_ENS_Community submitted: ENST00000215838, GRID_Transcript_RefSeq: NM_000355.2, GRID_Transcript_ENS_used_on_Production: ENST00000215838

Created: 17 Apr 2018, 12:12 p.m.

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Comment when marking as ready: two green expert reviews and many publications

Created: 10 May 2016, 12:42 p.m.

Green List (high evidence)

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Transcobalamin II deficiency; can have a presentation similar to severe combined immunodeficiency; pancytopenia; neutropenic colitis; Agammaglobulinemia; megaloblastic bone marrow; thrombocytopenia; neutropenia; failure to thrive; hypotonia, myoclonic like movements, pallor, purpura, anaemia, thrombocytopenia, megaloblastosis, aplastic bone marrow.

Publications

• PMID: 24305960
• 7980584
• 7849710
• 20352340
• 18956254

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• 24305960

Comment when marking as ready: Gene added by a reviewer, and rated green by two reviewers. Ready for Version 1.

Created: 17 Dec 2015, 10:58 a.m.