Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: SYKThe rating of this gene has been updated following NHS Genomic Medicine Service approval.Created: 8 Mar 2022, 10:59 a.m. | Last Modified: 8 Mar 2022, 10:59 a.m.
Panel Version: 2.532
Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update - PMID:33782605 report distinct monoallelic GoF variants in 5 families (6 individuals) with immune dysregulation and inflammation. Expression of one of these variants in a mouse model replicated aspects of the human immunopathology.Created: 26 Apr 2021, 2:42 p.m. | Last Modified: 26 Apr 2021, 2:42 p.m.
Panel Version: 2.414
5 unrelated patients with monoallelic missense variants in SYK with immune deficiency, multi-organ inflammatory disease such as colitis, arthritis and dermatitis, and diffuse large B cell lymphomas. 2 patients were confirmed de novo, others were undetermined. Variants exhibited a GoF effect in functional studies. A knock-in mouse model of a patient variant recapitulated aspects of the human disease.
Sufficient evidence for diagnostic use given the functional data.Created: 19 Apr 2021, 8:33 a.m. | Last Modified: 19 Apr 2021, 8:33 a.m.
Panel Version: 2.413
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Immune dysregulation and systemic inflammation
Publications
Variants in this GENE are reported as part of current diagnostic practice
Wang et al. identified six patients from unrelated kindreds with monoallelic SYK variants causing immunodeficiency and a multiorgan inflammatory disease. The variants were proven to be functionally gain-of-function. Functional GOF was confirmed in knock-in mouse experiments.
Sources: LiteratureCreated: 10 Apr 2021, 7:08 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
immunodeficiency; hypogammaglobulinemia; multi-organ inflammatory disease
Publications
Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Tag Q2_21_rating was removed from gene: SYK.
Source Expert Review Green was added to SYK. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Tag Q2_21_rating tag was added to gene: SYK.
Gene: syk has been classified as Amber List (Moderate Evidence).
gene: SYK was added gene: SYK was added to Primary immunodeficiency. Sources: Literature Mode of inheritance for gene: SYK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SYK were set to 33782605 Phenotypes for gene: SYK were set to immunodeficiency; hypogammaglobulinemia; multi-organ inflammatory disease Penetrance for gene: SYK were set to unknown Mode of pathogenicity for gene: SYK was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: SYK was set to AMBER