Skeletal dysplasia

Gene: KIAA1217

Red List (low evidence)

inheritance likely monoallelic - the reported comp het variant is present at 1.3% carrier f in asian population (the proband was from Chinese cohort).
majority of variants identified are present on gnomAD, located at non-conserved residues, some inherited from unaffected parents. The gnomAD missense constraint score for the gene is 0.29. Even if there was an association with vertebral defects it would currently be impossible to classify variants for clinical utility.

Created: 30 Jan 2021, 1:33 p.m. | Last Modified: 30 Jan 2021, 1:33 p.m.

Panel Version: 2.80

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
vertebral malformations

Publications

• 32369272

I don't know

The rating of this gene has been updated following NHS Genomic Medicine Service approval. It has been demoted to red as per reviewer recommendation.

Created: 6 Mar 2022, 5:41 p.m. | Last Modified: 6 Mar 2022, 5:41 p.m.

Panel Version: 2.176

Comment on list classification: After consultation with the Genomics England clinical team rating this gene amber. Although there are 10 cases reported, the mode of inheritance and level of penterance is not clear, and it would be useful to have more information prior to diagnostic use

Created: 1 Sep 2020, 10:38 a.m. | Last Modified: 1 Sep 2020, 10:38 a.m.

Panel Version: 2.15

PMID: 32369272 - Al Dhaheri et al 2020 - 10 unrelated probands with vertebral malformations.  1 proband was compound heterozygous for variants in KIAA1217, the others were all heterozygous. 9 out of 11 variants are found in gnomad but a low allele frequency.  In 3 patients (including the compound het) the variants were inherited from an unaffected parent, in the other 7 patients parental DNA was not available. Not associated with any phenotype in OMIM or Gene2Phenotype.
Sources: Literature

Created: 1 Sep 2020, 10:35 a.m. | Last Modified: 1 Sep 2020, 10:39 a.m.

Panel Version: 2.15

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
vertebral malformations

Publications

• 32369272