Primary ciliary disorders

Gene: GAS2L2

Comment on list classification: Promoting to Green based on expert review. Gene has been updated with Ensembl gene identifiers.

Created: 4 May 2020, 1:51 p.m. | Last Modified: 4 May 2020, 1:51 p.m.

Panel Version: 1.24

Comment on list classification: Demoting to Amber for now as this gene currently has no Ensembl IDs in PanelApp. Will promote to green again when this issue is resolved.

Created: 7 Nov 2019, 10:29 a.m. | Last Modified: 7 Nov 2019, 10:29 a.m.

Panel Version: 1.22

Comment on list classification: After consultation with the Genomics England clinical team it was decided to change the rating of this gene from Amber to Green based on the additional green expert review.

Created: 6 Nov 2019, 4:12 a.m. | Last Modified: 6 Nov 2019, 4:12 a.m.

Panel Version: 1.21

Green List (high evidence)

On CGGL Royal Brompton PCD/Bronchiectasis/Ciliopathies Panel.
Limited, but good evidence in literature:
Only two patients described so far: Bustamante-Marin et al 2019 Am J Hum Genet 2019 104(2):229-245
They found homozygous frameshift in 56-year old with clinical PCD (two untested sibs also had PCD, and unaffected sib is carrier). Also second unrelated PCD patient, compound heterozygous with same frameshift and partial exon 5 /exon 6 deletion.
Also in this study: Loss of GAS2L2 disrupts cilia beat frequency and orientation, and GAS2L2 Mouse KO develops PCD-like phenotype

Created: 24 Sep 2019, 4:23 p.m. | Last Modified: 24 Sep 2019, 4:23 p.m.

Panel Version: 1.19

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
OMIM 618449 Ciliary dyskinesia, primary, 41

Publications

• 30665704

Variants in this GENE are reported as part of current diagnostic practice

I don't know

PMID: 30665704 reports two unrelated individuals with clinical features of primary ciliary dyskinesia, one of whom had a homozygous frameshift variant in GAS2L2; the other was a compound heterozygote for the same variant and an intragenic deletion in GAS2L2. Cultured cells from one of the patients showed evidence of ciliary dysfunction and there was functional evidence of ciliary dysfunction in Xenopus and mouse knockouts.
Sources: Expert Review

Created: 24 Jan 2019, 12:54 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Primary ciliary dyskinesia

Publications

• PMID: 30665704