Prepair 1000+

Gene: SLC26A2

Comment when marking as ready: ClinGen has curated this gene for 4 split disease entities (see Mondo terms) when curating consider genotype-phenotype

Created: 12 Dec 2024, 1:58 a.m. | Last Modified: 12 Dec 2024, 1:58 a.m.

Panel Version: 1.673

Comment on phenotypes: ClinGen has split this gene for 4 disease entities as per the Mondo terms. Curation of variants will need to consider the spectrum.

Created: 12 Dec 2024, 1:56 a.m. | Last Modified: 12 Dec 2024, 1:56 a.m.

Panel Version: 1.669

Green List (high evidence)

Well established gene disease association causing skeletal abnormalities of varying severity.
Variants in this gene have been shown to cause achondrogenesis type 1B, atelosteogenesis type 2, diastrophic dysplasia, and recessive multiple epiphyseal dysplasia, which comprise a spectrum of phenotypes (depending on level of residual sulfate transport). Onset/features can often be observed neonatally.
Mouse models present for some phenotypes, and functional studies are present.

Homozygosity or compound heterozygosity for stop codons or transmembrane domain substitutions mostly result in achondrogenesis type IB, whereas other structural or regulatory variants usually result in one of the less severe phenotypes (PMID: 8723100)

Unsure of phenotypes to list under condition. Clingen includes curations for:
diastrophic dysplasia MONDO:0009107
multiple epiphyseal dysplasia MONDO:0016648
atelosteogenesis type II MONDO:0009727
achondrogenesis type IB MONDO:0010966
OMIM phenotypes (6) listed above.

Created: 11 Dec 2024, 5:43 a.m. | Last Modified: 11 Dec 2024, 5:44 a.m.

Panel Version: 1.633

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Achondrogenesis Ib MIM#600972; Atelosteogenesis, type II MIM#256050; De la Chapelle dysplasia MIM#256050; Diastrophic dysplasia MIM#222600; Diastrophic dysplasia, broad bone-platyspondylic variant MIM#222600; Epiphyseal dysplasia, multiple, 4 MIM#226900

Publications

• 20301483
• 20301689
• 11241838
• 8723100