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Primary immunodeficiency

Gene: SYK

Amber List (moderate evidence)

SYK (spleen associated tyrosine kinase)
EnsemblGeneIds (GRCh38): ENSG00000165025
EnsemblGeneIds (GRCh37): ENSG00000165025
OMIM: 600085, Gene2Phenotype
SYK is in 1 panel

3 reviews

Arina Puzriakova (Genomics England Curator)

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

Zornitza Stark (Australian Genomics)

Green List (high evidence)

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

Boaz Palterer (University of Florence)

I don't know

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: Literature
Created: 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

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Amber
Phenotypes
  • immunodeficiency
  • hypogammaglobulinemia
  • multi-organ inflammatory disease
Tags
Q2_21_rating
OMIM
600085
Clinvar variants
Variants in SYK
Penetrance
unknown
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
Panels with this gene

History Filter Activity

26 Apr 2021, Gel status: 2

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag Q2_21_rating tag was added to gene: SYK.

26 Apr 2021, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: syk has been classified as Amber List (Moderate Evidence).

10 Apr 2021, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes, Set penetrance, Set mode of pathogenicity

Boaz Palterer (University of Florence)

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