Hypogonadotropic hypogonadism (GMS)
Gene: FGF17After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains AMBER. The additional comments from GLH's is "Gene should stay amber./ Borderline. Miraoui et al 2013 (PMID: 23643382): 2 males with missense variants, female with missense variant and variants in 3 other genes, functional characterisation of variants, mouse model. Cassatella et al 2018 (PMID: 29419413): missense variant classified as a VUS. Amato et al 2019 (PMID: 31200363): 1 case with missense variant. Men et al 2019 (PMID: 31748124): indel and two missense variants, GnomAD frequency for one of the missense changes higher than expected."Created: 31 Jan 2023, 5:03 p.m. | Last Modified: 31 Jan 2023, 5:03 p.m.
Panel Version: 2.5
Updating tags to be Q3_22_expert_review and Q3_22_rating so that gene is included in the next GMS report (Oct 2022)Created: 5 Oct 2022, 11:36 p.m. | Last Modified: 5 Oct 2022, 11:36 p.m.
Panel Version: 1.54
Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM but not in Gene2Phenotype.
PMID: 23643382 identfied 3 cases with variants in the FGF17 gene. However, 1 of these cases have variants in other genes as well (FLRT3, HS6ST1 and FGFR1).
Based on the available evidence variants in this gene contribute to disease with variable penetrance. This gene has been given an Amber rating until further evidence is available.Created: 1 Apr 2021, 1 p.m. | Last Modified: 1 Apr 2021, 1 p.m.
Panel Version: 1.41
PMID: 23643382 - 3 individuals with Kallman syndrome or idiopathic hypogonadotropic hypogonadism (IHH). Functional studies on missense showed reduced protein expression and destabilization, one individual had additional variants in other genes.
PMID: 31748124 - 3 individuals with IHH, where two individuals inherited variants from unaffected parents.
Sources: Expert listCreated: 15 Jul 2020, 7:45 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Hypogonadotropic hypogonadism 20 with or without anosmia, MIM# 615270
Publications
Tag Q3_22_rating was removed from gene: FGF17. Tag Q3_22_expert_review was removed from gene: FGF17.
Tag Q2_21_expert_review was removed from gene: FGF17. Tag Q3_22_rating tag was added to gene: FGF17. Tag Q3_22_expert_review tag was added to gene: FGF17.
Gene: fgf17 has been classified as Amber List (Moderate Evidence).
Tag Q2_21_expert_review tag was added to gene: FGF17.
Phenotypes for gene: FGF17 were changed from Hypogonadotropic hypogonadism 20 with or without anosmia, MIM# 615270 to Hypogonadotropic hypogonadism 20 with or without anosmia, OMIM:615270
gene: FGF17 was added gene: FGF17 was added to Hypogonadotropic hypogonadism idiopathic. Sources: Expert list Mode of inheritance for gene: FGF17 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: FGF17 were set to 23643382; 31748124 Phenotypes for gene: FGF17 were set to Hypogonadotropic hypogonadism 20 with or without anosmia, MIM# 615270 Penetrance for gene: FGF17 were set to Incomplete Review for gene: FGF17 was set to AMBER