Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: STXBP2

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, 4:39 p.m. | Last Modified: 14 Oct 2020, 4:39 p.m.

Panel Version: 2.320

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, 4:39 p.m. | Last Modified: 14 Oct 2020, 4:39 p.m.

Panel Version: 2.319

The following PubMed IDs were added to entity STXBP2: 19804848;30557712;22451424;19884660;29776323. These publications have been associated with OMIM phenotype MIM#613101, which is listed for this entity, by the immunedysregulation 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

• 19804848
• 30557712
• 22451424
• 19884660
• 29776323

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)

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): STXBP2 .PanelApp HGNC gene symbol check: STXBP2 . IUIS Disease: STXBP2 / Munc18-2 deficiency (FHL5) . IUIS Inheritance: AR or AD .T cells: N/A, .B cells: Normal, .IUIS Other affected cells: N/A. IUIS Associated features: Fever, HSM, cHLH, cytopenias, enteropathy. IUIS Major category: Diseases of Immune Dysregulation. IUIS Subcategory: Familial Hemophagocytic Lymphohistiocytosis (FHL syndromes)

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

from GeneReview PMID:20301617: 16% in Central Europeans, Turks, and Saudis (PMID:19804848) and approx 20% in North Americans with FHL PMID:20301617 are FHL5.

Created: 30 Apr 2018, 11:12 a.m.

Changed status from Amber to Green, there are more than 3 unrelated cases to support the phenotype Familial hemophagocytic lymphohistiocytosis-5 (FHL5)caused by homozygous or compound heterozygous mutation in the syntaxin-binding protein-2 gene (STXBP2). From OMIM Publications include: 8 unrelated probands with familial hemophagocytic lymphohistiocytosis (FHL) mapped to STXBP2 in 2 Saudi Arabian and 6 Turkish consanguineous families, zur Stadt et al. (2009) PMID:19804848 sequenced the candidate gene STXBP2 and identified homozygous mutations in STXBP2 in all 8 patients. Also, in affected members of 6 consanguineous families Cote et al. (2009) PMID: 19884660 sequenced the STXBP2 gene and identified homozygosity for the P477L mutation (601717.0001) in 3 Saudi Arabian families and for the IVS14 splice site mutation (601717.0003) in 3 families of Turkish, Palestinian Arab, and Iranian origin, respectively. In PMID: 20798128 Cetica et al. (2010) analyzed the STXBP2 gene in 28 FHL families in which mutations in known FHL genes had been excluded by sequence analysis, and identified homozygosity for 4 different missense mutations in the STXBP2 gene in 4 (14%) of the 28 families, originating from Italy, England, Kuwait, and Pakistan, respectively.

Created: 30 Apr 2018, 11:09 a.m.

Comment on publications: Added publications to support role of STXBP2 variants in Hemophagocytic lymphohistiocytosis, familial, 5

Created: 30 Apr 2018, 10:59 a.m.

From OMIM Familial hemophagocytic lymphohistiocytosis-5 (FHL5) is caused by homozygous or compound heterozygous mutation in the syntaxin-binding protein-2 gene (STXBP2; 601717) on chromosome 19p13.

Created: 30 Apr 2018, 10:55 a.m.

Comment on phenotypes: added OMIM MIMid and synonyms

Created: 30 Apr 2018, 10:49 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: 19 Apr 2018, 1:59 p.m.

Original metadata downloaded from ESID Registry. ESID_Gene_original: STXBP2 (Munc 18-2), PanelApp HGNC gene symbol check: STXBP2, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Diseases of immune dysregulation / Hemophagocytic Lymphohistiocytosis (HLH) / Familial hemophagocytic lymphohistiocytosis syndromes (FHLH)

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

Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: STXBP2, GRID_Gene_Symbol: STXBP2, GRID_Transcript_ENS_Community submitted: ENST00000221283, GRID_Transcript_RefSeq: NM_006949.2, GRID_Transcript_ENS_used_on_Production: ENST00000221283

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