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Fetal anomalies

Gene: COG4

Green List (high evidence)
COG4 (component of oligomeric golgi complex 4)
EnsemblGeneIds (GRCh38): ENSG00000103051
EnsemblGeneIds (GRCh37): ENSG00000103051
OMIM: 606976, Gene2Phenotype
COG4 is in 12 panels

1 review

Rebecca Foulger (Genomics England curator)

Green List (high evidence)

The evidence for Saul-Wilson syndrome (MIM:618150) comes from one 2018 paper (PMID:30290151): Ferreira et al. (PMID:30290151, 2018) identified 2 different de novo heterozygous vaiants in the COG4 gene in 14 individuals, c.1546G-A and c.1546G-C both of which give rise to an identical missense mutation (G516R). Functional analysis shows that a stable protein is produced and, despite Golgi collapse, glycosylation is relatively normal. Given the DD-G2P Disease confidence rating is 'probable' (March 2019), only a missense variant has been reported, and functional evidence doesn't yet show the effect of the protein alteration, I have kept the MOI for COG4 on the Fetal anomalies panel as biallelic (for the confirmed glycosylation disorder) and not included the monoallelic Saul-Wilson syndrome on the panel at this stage.
Created: 24 Apr 2019, 11:29 a.m.
COG4 is Green on the fetal panel based on 'confirmed' rating for a biallelic glycosylation disorder (COG4-CDG) and expert clinical review. A probable gene:disease disorder also exists in DD-Gene2Phenotype: Saul-Wilson syndrome. DDG2P Disease confidence: probable. DDG2P mode of pathogenicity/mutation consequence: all missense/in frame, gain of function. DDG2P mode of inheritance: monoallelic.

Saul-Wilson syndrome is a rare form of primordial dwarfism with severe pre-and postnatal growth retardation, and characteristic facial and radiographic features (PMID:30290151). Fetal relevance was confirmed by Anna de Burca but the evidence requires further investigation before the MOI is expanded to include monoallelic variants.
Created: 24 Apr 2019, 11:26 a.m.
This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Confirmed that phenotype is fetally-relevant: keep on the Fetal anomalies panel as a Green gene.
Created: 24 Mar 2019, 4:30 p.m.
DDG2P rating in original PAGE list: Confirmed for COG4-CDG
Created: 11 Dec 2018, 9:04 a.m.
Created: 11 Dec 2018, 9:04 a.m.

Panel version: 0.199

History Filter Activity

11 Jun 2019, Gel status: 3

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

Gene: cog4 has been classified as Green List (High Evidence).

30 Apr 2019, Gel status: 4

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for gene: COG4 were changed from COG4-CDG to COG4-CDG; Saul-Wilson syndrome, 618150

24 Apr 2019, Gel status: 4

Set publications

Rebecca Foulger (Genomics England curator)

Publications for gene: COG4 were set to

8 Nov 2018, Gel status: 4

Created, Added New Source, Set mode of inheritance, Set Phenotypes

Rebecca Foulger (Genomics England curator)

gene: COG4 was added gene: COG4 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: COG4 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: COG4 were set to COG4-CDG