Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: SMARCAL1

Comment on phenotypes: Previous (overwritten) phenotypes: Schimke disease;Short stature, spondiloepiphyseal dysplasia, intrauterine growth retardation, nephropathy, bacterial, viral, fungal infections, may present as SCID, bone marrow failure;Combined immunodeficiencies with associated or syndromic features

Created: 4 Mar 2024, 5:21 p.m. | Last Modified: 4 Mar 2024, 5:21 p.m.

Panel Version: 4.193

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, 4:25 p.m. | Last Modified: 14 Oct 2020, 4:25 p.m.

Panel Version: 2.312

The following PubMed IDs were added to gene SMARCAL1 (OMIM gene MIM#606622): 17089404;11799392. 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 as >3 cases of likely disease causing variants.

Created: 16 May 2018, 10:49 a.m.

In OMIM this gene is associated with Schimke immunoosseous dysplasia. One of the diagnostic features of this disorder is T-cell immunodeficiency. OMIM reports that Boerkoel et al. (2002) (PMID: 11799392) determined that mutations in SMARCAL1 are responsible for SIOD. They looked at patients from 26 unrelated families and observed that affected individuals from 13 of 23 families with severe disease had 2 alleles with nonsense, frameshift, or splicing mutations, whereas affected individuals from 3 of 3 families with milder disease had a missense mutation on each allele. These observations indicated that some missense mutations allow retention of partial SMARCAL1 function and thus cause milder disease. Clewing et al. (2007)(PMID: 17089404) stated that 43 different mutations in the SMARCAL1 gene had been identified. They found that in 4 patients with a presumed monoallelic, heterozygous mutation in the SMARCAL1 gene, expressed RNA and/or protein from the other allele was not found, suggesting that in fact these 4 patients had biallelic SMARCAL1 mutations, though the second mutation was not found. Gene2Phenotype has a confirmed disease association between SMARCAL1 and Schimke immuno-osseous dysplasia. Rating this gene green as >3 cases of likely disease causing variants.

Created: 16 May 2018, 10:48 a.m.

Comment on phenotypes: Added MIM number to Schimke immunoosseous dysplasia

Created: 16 May 2018, 8:48 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• 17089404
• 11799392

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): SMARCAL1 .PanelApp HGNC gene symbol check: SMARCAL1 . IUIS Disease: Schimke Immuno-osseous Dysplasia . IUIS Inheritance: AR .T cells: Low CD8, Nl CD4, absent MHC I on lymphocytes, .B cells: Normal, .IUIS Other affected cells: N/A. IUIS Associated features: Short stature, spondiloepiphyseal dysplasia, intrauterine growth retardation, nephropathy, bacterial, viral, fungal infections, may present as SCID, bone marrow failure. IUIS Major category: Combined immunodeficiencies with associated or syndromic features. IUIS Subcategory: Immuno-osseous Dysplasias

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: 19 Apr 2018, 3:01 p.m.

Original metadata downloaded from ESID Registry. ESID_Gene_original: SMARCAL1, PanelApp HGNC gene symbol check: SMARCAL1, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Other well defined PIDs / Schimke disease / Schimke disease

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

Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: SMARCAL1, GRID_Gene_Symbol: SMARCAL1, GRID_Transcript_ENS_Community submitted: ENST00000357276, GRID_Transcript_RefSeq: NM_014140.3, GRID_Transcript_ENS_used_on_Production: ENST00000357276

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