Skeletal dysplasia
Gene: SCUBE3

SCUBE3 (signal peptide, CUB domain and EGF like domain containing 3)
EnsemblGeneIds (GRCh38): ENSG00000146197
EnsemblGeneIds (GRCh37): ENSG00000146197
OMIM: 614708, Gene2Phenotype
SCUBE3 is in 5 panels

4 reviews

Sarah Leigh (Genomics England Curator)

Green List (high evidence)

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.
Created: 1 Apr 2021, 10:58 a.m. | Last Modified: 14 Oct 2021, 10:32 a.m.

Panel Version: 2.137

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

Created: 1 Apr 2021, 10:55 a.m.
Last Modified: 14 Oct 2021, 10:32 a.m.
Panel version: 2.85

Zornitza Stark (Australian Genomics)

Green List (high evidence)

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

33308444

Variants in this GENE are reported as part of current diagnostic practice

Created: 7 Jan 2021, 9:56 a.m.
Last Modified: 7 Jan 2021, 9:56 a.m.
Panel version: 2.42

Arina Puzriakova (Genomics England Curator)

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

Created: 6 Nov 2020, 5:39 p.m.
Last Modified: 6 Nov 2020, 5:39 p.m.
Panel version: 2.30

Eleanor Williams (Genomics England Curator)

The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Created: 6 Mar 2022, 6:30 p.m. | Last Modified: 6 Mar 2022, 6:30 p.m.

Panel Version: 2.184

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

Created: 14 Jan 2020, 3:47 p.m.
Last Modified: 14 Jan 2020, 3:48 p.m.
Panel version: 2.184

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

Expert Review Green

Phenotypes

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

OMIM

614708

Clinvar variants

Variants in SCUBE3

Penetrance

unknown

Publications

33308444

Panels with this gene

History Filter Activity

6 Mar 2022, Gel status: 3

Removed Tag

Eleanor Williams (Genomics England Curator)

Tag Q2_21_rating was removed from gene: SCUBE3.

6 Mar 2022, Gel status: 3

Added New Source, Status Update

Eleanor Williams (Genomics England Curator)

Source Expert Review Green was added to SCUBE3. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

14 Oct 2021, Gel status: 2