Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: RBCK1

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, 4:20 p.m. | Last Modified: 14 Oct 2020, 4:20 p.m.

Panel Version: 2.304

The following PubMed IDs were added to gene RBCK1 (OMIM gene MIM#610924): 23798481;610924. 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

• 23798481
• 610924

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)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
bacterial infections, autoinflammation, amylopectinosis

Publications

• 23104095

Comment on list classification: Associated with phenotype in OMIM and not in Gen2Phen. At least 8 variants identified in unrelated cases, however, only 2 cases had Polyglucosan body myopathy 1 with immunodeficiency.

Created: 9 May 2018, 2:55 p.m.

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

Comment on list classification: Changed Amber to Green from external expert review and further publications to support gene-disease association (more than three cases with immunodeficiency

Created: 5 Jul 2018, 10:54 a.m.

Krenn M et al (2018) PMID: 29260357 describe two new patients with pathogenic mutations in the RBCK1 gene expanding the total number of known families with this condition in the literature from 12 to 14. They confirmed the few previous reports insofar as both a myopathy and an immunological phenotype are part of the clinical spectrum of RBCK1-associated disease. It was suggested that the exact localization of the mutation within the gene might be responsible for the specific phenotype, with N-terminal mutations causing severe immunological dysfunction and mutations in the middle or C-terminal part leading to a myopathy phenotype. They reported the clinical, immunological and genetic findings of two unrelated individuals suffering from a childhood-onset RBCK1-asscociated disease caused by the same homozygous truncating mutation (NM_031229.2:c.896_899del, p.Glu299Valfs*46) in the middle part of the RBCK1 gene. The patients suffered from a myopathy with cardiac involvement, but in contrast to previous reports on mutations in this part of the gene, also displayed signs of autoinflammation and immunodeficiency. The report suggests that RBCK1 mutations at locations that were previously thought to lack immunological features may also present with immunological dysfunction later in the disease course.

Created: 5 Jul 2018, 10:52 a.m.

Comment on publications: Added publications to support gene-disease association, and upgrading of the gene to Green.

Created: 5 Jul 2018, 10:52 a.m.

OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): HOIL1 (RBCK1) .PanelApp HGNC gene symbol check: RBCK1 . IUIS Disease: HOIL1 deficiency . IUIS Inheritance: AR .T cells: N/A, .B cells: Normal, decreased memory B cells, .IUIS Other affected cells: N/A. IUIS Associated features: Bacterial infections, autoinflammation, amylopectinosis . IUIS Major category: Combined immunodeficiencies with associated or syndromic features. IUIS Subcategory: Other Combined immunodeficiencies with associated or syndromic features

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

This gene was absent from the original PanelApp PID panel dataset (review April 2018). However it was listed in 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: HOIL1, PanelApp HGNC gene symbol check: RBCK1, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Autoinflammatory disorders / Other autoinflammatory diseases with known genetic defect / Other autoinflammatory diseases with known genetic defect; Defects in innate immunity / HOIL1 deficiency / HOIL1 deficiency

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

Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: RBCK1, GRID_Gene_Symbol: RBCK1, GRID_Transcript_ENS_Community submitted: ENST00000356286, GRID_Transcript_RefSeq: NM_031229.2, GRID_Transcript_ENS_used_on_Production: ENST00000356286

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