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Skeletal dysplasia v8.20 SIK3 Ida Ertmanska reviewed gene: SIK3: Rating: AMBER; Mode of pathogenicity: None; Publications: 22318228, 30232230; Phenotypes: Spondyloepimetaphyseal dysplasia, Krakow type, OMIM: 618162, spondyloepimetaphyseal dysplasia, Krakow type, MONDO:0032571; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v8.20 SIK3 Ida Ertmanska Tag watchlist tag was added to gene: SIK3.
Skeletal dysplasia v8.17 SIK3 Sarah Graham reviewed gene: SIK3: Rating: GREEN; Mode of pathogenicity: None; Publications: 30232230, 22318228; Phenotypes: Spondyloepimetaphyseal dysplasia, Krakow type, OMIM:618162; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal dysplasia v8.17 SIK3 Eleanor Williams Classified gene: SIK3 as Amber List (moderate evidence)
Skeletal dysplasia v8.17 SIK3 Eleanor Williams Added comment: Comment on list classification: Promoted to amber since there is one published case plus a supportive mouse model. Following up with evidence from UK NHS cases and the rating maybe reviewed.
Skeletal dysplasia v8.17 SIK3 Eleanor Williams Gene: sik3 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v8.16 SIK3 Eleanor Williams Added comment: Comment on phenotypes: OMIM phenotype accessed on 8th October 2025
Skeletal dysplasia v8.16 SIK3 Eleanor Williams Phenotypes for gene: SIK3 were changed from to ?Spondyloepimetaphyseal dysplasia, Krakow type, OMIM:618162; spondyloepimetaphyseal dysplasia, Krakow type, MONDO:0032571
Skeletal dysplasia v8.15 SIK3 Eleanor Williams Classified gene: SIK3 as Amber List (moderate evidence)
Skeletal dysplasia v8.15 SIK3 Eleanor Williams Gene: sik3 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v7.16 SIK3 Ronnie Wright gene: SIK3 was added
gene: SIK3 was added to Skeletal dysplasia. Sources: NHS GMS
Mode of inheritance for gene: SIK3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SIK3 were set to 30232230; 22318228
Penetrance for gene: SIK3 were set to Complete
Review for gene: SIK3 was set to AMBER
gene: SIK3 was marked as current diagnostic
Added comment: Literature:
PMID:30232230 - 2 sibs affected with metaphyseal dysplasia, alongside other phenotypes (developmental delay with brain MRI abnormalities, a severe unclassified immunodeficiency) homozygous for NM_001366686.3(SIK3):c.559C>T p.(Arg187Cys), referred to as R129C in the publication - shown to affect kinase activity

Clinical/diagnostic testing:
Homozygous duplication (Exon 2-4 - no RNA but predicted out of frame insertion) in GMS clinical testing (off panel/untiered) in patient with with spondylometaphyseal skeletal dysplasia alongside global developmental delay, focal seizures, tetralogy of fallot (CVA-120418-1)

A possible 3rd family would provide support for green rating (details unknown- ?prenatally detected skeletal anomalies, see SIK3 review in fetal anomalies gene panel (https://panelapp.genomicsengland.co.uk/panels/478/gene/SIK3/)

Animal Model:
Association with skeletal dysplasia supported by mouse model evidence PMID:22318228
Sources: NHS GMS