Hypogonadotropic hypogonadism (GMS)
Gene: SPRY4After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains AMBER. The additional comments from GLH's is "Variants in Miraoui et al 2013 in gnomAD at frequency higher than expected. Amato et al 2019: missense variant in patient with nCHH who was also heterozygous for a IGSF10 missense variant. Indirili et al 2019 (PMID: 31781046): missense variant identified in a male with IHH and anosmia. recent curation suggessts change in classification from red to Amber - NOT TO GREEN"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 p.m. | Last Modified: 5 Oct 2022, 11 p.m.
Panel Version: 1.54
Comment on list classification: Promoted from Red to Amber.
PMID:23643382 - 14 unrelated cases had variants in SPRY4, 3 cases had variants in other genes (DUSP6 and FGFR1).
PMID: 32389901 - 1 cases had variants in SPRY4 and PLXNA1.
Based on the available evidence, this variants in this gene may contribute to disease. Therefore this gene has been promoted from Red to Amber.Created: 1 Apr 2021, 1:43 p.m. | Last Modified: 1 Apr 2021, 1:43 p.m.
Panel Version: 1.31
Comment on list classification: Changed the rating from green to red, before promoting this panel to version 1 due to internal discussion. Because this gene only has monoallelic variants reported, it may be that studies did not examine fully whether variants in other genes had a second variant and therefore monoallelic variants in this gene may not provide a complete diagnosis.Created: 28 Oct 2016, 1:26 p.m.
Comment when marking as ready: Associated with phenotype in OMIM, not in G2P. Found in 1/4 sources. Three reviewers recommend Green. Eight variants reported, at least six monogenic and two polygenic cases reported PMID 23643382Created: 12 Oct 2016, 1:45 p.m.
Tag Q3_22_rating was removed from gene: SPRY4. Tag Q3_22_expert_review was removed from gene: SPRY4.
Tag Q2_21_expert_review was removed from gene: SPRY4. Tag Q3_22_rating tag was added to gene: SPRY4. Tag Q3_22_expert_review tag was added to gene: SPRY4.
gene: SPRY4 was added gene: SPRY4 was added to Hypogonadotropic hypogonadism idiopathic. Sources: Expert Review Amber,Radboud University Medical Center, Nijmegen,Expert list,Literature monogenic-polygenic, Q2_21_expert_review tags were added to gene: SPRY4. Mode of inheritance for gene: SPRY4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: SPRY4 were set to 23643382; 32389901 Phenotypes for gene: SPRY4 were set to Hypogonadotropic hypogonadism 17 with or without anosmia, OMIM:615266 Penetrance for gene: SPRY4 were set to Complete