Fetal anomalies
Gene: SCUBE3This gene and phenotype were reviewed during a meeting on 2nd March 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, (North Thames GLH), and Stephanie Allen, Denise Williams, Anna de Burca and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene.Created: 5 May 2023, 3 p.m. | Last Modified: 5 May 2023, 3 p.m.
Panel Version: 3.8
The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.Created: 10 Oct 2023, 3:39 p.m. | Last Modified: 10 Oct 2023, 3:39 p.m.
Panel Version: 3.111
Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. PMID 33308444 reports eight SCUBE variants in nine unrelated families, including eighteen affected members. In vtro studies demonstrated a variable impact of disease-causing variants on transcript processing, protein secretion and function, resulting in dysregulation on bone morphogenetic protein (BMP) signaling and a Scube3−/− mouse showed shared phenotypic features with OMIM:619184. Prenatal growth retardation was evident in 8/11 relevant cases.Created: 1 Apr 2021, 10:58 a.m. | Last Modified: 14 Oct 2021, 10:21 a.m.
Panel Version: 1.727
Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.Created: 1 Apr 2021, 10:55 a.m. | Last Modified: 1 Apr 2021, 10:55 a.m.
Panel Version: 2.85
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Eighteen affected individuals from nine unrelated families reported with a consistent phenotype characterised by reduced growth, skeletal features, distinctive craniofacial appearance, and dental anomalies. Mouse model recapitulated phenotype.Created: 7 Jan 2021, 9:56 a.m. | Last Modified: 7 Jan 2021, 9:56 a.m.
Panel Version: 2.42
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Short stature; skeletal abnormalities; craniofacial abnormalities; dental anomalies
Publications
Variants in this GENE are reported as part of current diagnostic practice
Comment on list classification: Confirmed with Stephanie Allen that the GMS Fetal expert group determined there is sufficient evidence to classify this gene as Green (9th May 2023).Created: 10 May 2023, 10:44 a.m. | Last Modified: 10 May 2023, 10:44 a.m.
Panel Version: 3.80
The to_be_confirmed_NHSE tag has been added, as further NHSE review is required before promoting this gene to green.Created: 30 Jan 2023, 4:26 p.m. | Last Modified: 30 Jan 2023, 4:26 p.m.
Panel Version: 2.10
Comment on list classification: Rating Red as currently only one case reported with a potentially pathogenic variant associated with skeletal dysplasia. Additional cases required to corroborate causality.Created: 6 Nov 2020, 5:39 p.m. | Last Modified: 6 Nov 2020, 5:39 p.m.
Panel Version: 2.30
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, 4:59 p.m. | Last Modified: 5 Oct 2022, 4:59 p.m.
Panel Version: 1.974
A variant in this gene has been found in a 100K proband as potentially being the cause of a skeletal dysplasia.Created: 14 Jan 2020, 3:47 p.m. | Last Modified: 14 Jan 2020, 3:48 p.m.
Panel Version: 2.0
Tag Q2_23_promote_green was removed from gene: SCUBE3. Tag Q2_23_NHS_review was removed from gene: SCUBE3.
Source Expert Review Green was added to SCUBE3. Source NHS GMS was added to SCUBE3. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Gene: scube3 has been classified as Amber List (Moderate Evidence).
Tag to_be_confirmed_NHSE was removed from gene: SCUBE3. Tag Q3_22_rating was removed from gene: SCUBE3. Tag Q3_22_expert_review was removed from gene: SCUBE3.
Tag Q2_23_promote_green tag was added to gene: SCUBE3. Tag Q2_23_NHS_review tag was added to gene: SCUBE3.
Tag to_be_confirmed_NHSE tag was added to gene: SCUBE3.
Tag Q4_21_expert_review was removed from gene: SCUBE3. Tag Q3_22_rating tag was added to gene: SCUBE3. Tag Q3_22_expert_review tag was added to gene: SCUBE3.
Phenotypes for gene: SCUBE3 were changed from Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies OMIM:619184 to Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies OMIM:619184; short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies 2 MONDO:0030953
Tag Q4_21_expert_review tag was added to gene: SCUBE3.
Tag Q2_21_rating was removed from gene: SCUBE3.
gene: SCUBE3 was added gene: SCUBE3 was added to Fetal anomalies. Sources: Expert Review Amber,Other Q2_21_rating tags were added to gene: SCUBE3. Mode of inheritance for gene: SCUBE3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SCUBE3 were set to 33308444 Phenotypes for gene: SCUBE3 were set to Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies OMIM:619184 Penetrance for gene: SCUBE3 were set to unknown