Hypogonadotropic hypogonadism (GMS)

Gene: SPRY4

Amber List (moderate evidence)

SPRY4 (sprouty RTK signaling antagonist 4)
EnsemblGeneIds (GRCh38): ENSG00000187678
EnsemblGeneIds (GRCh37): ENSG00000187678
OMIM: 607984, Gene2Phenotype
SPRY4 is in 4 panels

8 reviews

Catherine Snow (Genomics England)

After 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

Eleanor Williams (Genomics England Curator)

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

Ivone Leong (Genomics England Curator)

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

Ellen McDonagh (Genomics England Curator)

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.

Sarah Leigh (Genomics England Curator)

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 23643382
Created: 12 Oct 2016, 1:45 p.m.

Richard Quinton (Newcastle University)

Green List (high evidence)

Mehul Dattani (UCL Institute of Child Health)

Green List (high evidence)

Louise IZATT (GSTT Clinical Genetics Service)

Green List (high evidence)

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Literature
  • Expert list
  • Radboud University Medical Center, Nijmegen
  • Expert Review Amber
Phenotypes
  • Hypogonadotropic hypogonadism 17 with or without anosmia, OMIM:615266
Tags
monogenic-polygenic
OMIM
607984
Clinvar variants
Variants in SPRY4
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

31 Jan 2023, Gel status: 2

Removed Tag, Removed Tag

Catherine Snow (Genomics England)

Tag Q3_22_rating was removed from gene: SPRY4. Tag Q3_22_expert_review was removed from gene: SPRY4.

5 Oct 2022, Gel status: 2

Removed Tag, Added Tag, Added Tag

Eleanor Williams (Genomics England Curator)

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.

14 Dec 2021, Gel status: 2

Created, Added New Source, Added Tag, Set mode of inheritance, Set publications, Set Phenotypes, Set penetrance

Ivone Leong (Genomics England Curator)

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