Disorders of sex development
Gene: FGFR2Removed the expert review tag as expert opinion from a member of the Genomics England clinical team was obtained.Created: 5 Oct 2022, 11:07 p.m. | Last Modified: 5 Oct 2022, 11:07 p.m.
Panel Version: 2.66
Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a phenotype in OMIM and Gene2Phenotype.
After consulting with the Genomics England Clinical Team, it was decided that this gene should be rated Amber. Helen Brittain (Genomics England):
"In the fetal cases the potential DSD phentoype is very mild and eclipsed by the skeletal / craniosynostosis presentation."Created: 19 Mar 2021, 12:51 p.m. | Last Modified: 19 Mar 2021, 12:51 p.m.
Panel Version: 2.45
PMID: 26362256 - 1 individual with craniosynostosis and XY sex reversal and a missense variant. Phenotype recapitulated using mouse model, concludes a LOF mechanism.
PMID: 18155190 - partial null mutant mouse model shows XY sex reversal
PMID: 2238701 - 4 fetuses with de novo mutations and a skeletal disorder 3/4 had clitoromegaly, last fetus only had radiograph available. p.(Met391Arg) is recurring, variants are supported by functional studies showing protein mislocalization
Mutations reported for all other FGFR2-related conditions have a GOF mechanism
Sources: Expert listCreated: 15 Jul 2020, 7:58 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
LADD syndrome 149730; Bent bone dysplasia syndrome 614592
Publications
Tag Q2_21_expert_review was removed from gene: FGFR2.
Tag Q2_21_expert_review tag was added to gene: FGFR2.
Gene: fgfr2 has been classified as Amber List (Moderate Evidence).
Publications for gene: FGFR2 were set to 26362256; 18155190
Publications for gene: FGFR2 were set to 26362256; 18155190; 2238701
Publications for gene: FGFR2 were set to 26362256; 18155190
Phenotypes for gene: FGFR2 were changed from LADD syndrome 149730; Bent bone dysplasia syndrome 614592 to LADD syndrome, OMIM:149730; Bent bone dysplasia syndrome, OMIM:614592
gene: FGFR2 was added gene: FGFR2 was added to Disorders of sex development. Sources: Expert list Mode of inheritance for gene: FGFR2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: FGFR2 were set to 26362256; 18155190 Phenotypes for gene: FGFR2 were set to LADD syndrome 149730; Bent bone dysplasia syndrome 614592 Review for gene: FGFR2 was set to GREEN