Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: SP110

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)

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, 4:26 p.m. | Last Modified: 14 Oct 2020, 4:26 p.m.

Panel Version: 2.313

The following PubMed IDs were added to gene SP110 (OMIM gene MIM#604457): 16648851. 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

Comment on list classification: Rating this gene green because there are more than 3 cases of plausible disease causing mutations.

Created: 16 May 2018, 11:27 a.m.

SP110 is associated with Hepatic venoocclusive disease with immunodeficiency in OMIM. OMIM reports that Roscioli et al. (2006) (PMID: 16648851) mapped the disorder to 2q36.3-q37.1 and then narrowed the region of interest down to a genomic region containing the SP110 gene. Screening of the coding exons of SP110 identified a homozygous single-base deletion, 642delC, in exon 5 in affected individuals from 4 families. In a fifth family no living affected individuals were available, but the consanguineous parents and unaffected children were shown to share a heterozygous single-base deletion, 40delC, in exon 2. That mutation was homozygous in archival material from the deceased member of family 5. Neither mutation was found in 50 unrelated Lebanese controls and no mutation was found in the coding regions of SP110 in 89 isolated cases of common variable immunodeficiency of European or Middle Eastern origin. Gene2Phenotype has no data for SP110. From a PubMed search a more recent publication was found (Wang et al 2012, PMID: 22982295) reporting a missense variant (a homozygous deletion/insertion variant) in an American child with Hepatic veno-occlusive disease with immunodeficiency with Hispanic parents . The mechanism by which this SP110 mutation associates with VODI is consistent with the normal length mutated SP110 protein being subject to enhanced proteosome degradation resulting in marked reductions in SP110 protein. Rating this gene green because there are more than 3 cases of plausible disease causing mutations.

Created: 16 May 2018, 11:26 a.m.

Comment on phenotypes: Added MIM number to Hepatic venoocclusive disease with immunodeficiency.

Created: 16 May 2018, 10:57 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• 16648851

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): SP110 .PanelApp HGNC gene symbol check: SP110 . IUIS Disease: Hepatic veno-occlusive disease with immunodeficiency (VODI) . IUIS Inheritance: AR .T cells: N/A, .B cells: Normal (decreased memory B cells), .IUIS Other affected cells: N/A. IUIS Associated features: Hepatic veno-occlusive disease, Susceptibility to Pneumocystis jirovecii pneumonia, CMV, candida, thrombocytopenia, hepatosplenomegaly, cerebrospinal leukodystrophy. 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.

Comment on publications: added missing PMID to support phenotype

Created: 13 Jun 2018, 10:40 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, 2:59 p.m.

Original metadata downloaded from ESID Registry. ESID_Gene_original: SP110, PanelApp HGNC gene symbol check: SP110, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Other well defined PIDs / VODI / Hepatic venoocclusive disease with immunodeficiency (VODI)

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

Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: SP110, GRID_Gene_Symbol: SP110, GRID_Transcript_ENS_Community submitted: ENST00000258381, GRID_Transcript_RefSeq: NM_080424.2, GRID_Transcript_ENS_used_on_Production: ENST00000258381

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