Fetal anomalies
Gene: TRAPPC12

TRAPPC12 (trafficking protein particle complex 12)
EnsemblGeneIds (GRCh38): ENSG00000171853
EnsemblGeneIds (GRCh37): ENSG00000171853
OMIM: 614139, Gene2Phenotype
TRAPPC12 is in 5 panels

3 reviews

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Created: 3 Mar 2022, 11:19 a.m. | Last Modified: 3 Mar 2022, 4:35 p.m.

Panel Version: 1.836

Comment on list classification: Maintaining Amber rating as currently there are not enough unrelated cases with a fetally-relevant phenotype to promote to Green. Added 'watchlist' tag.
Created: 20 Jan 2021, 12:38 p.m. | Last Modified: 20 Jan 2021, 12:38 p.m.

Panel Version: 1.162

Removed 'polygenic' tag as published cases revealed no evidence to indicate polygenic inheritance
Created: 20 Jan 2021, 12:36 p.m. | Last Modified: 20 Jan 2021, 12:36 p.m.

Panel Version: 1.158

- PMID: 32347653 (2020) - One family with recurrent fetal hydrocephalus affecting 3/4 pregnancies. Other variable anomalies included ventriculomegaly, minimal movement, and limb abnormalities (e.g. polydactyly, bilateral clubbed feet, abnormal hand positioning, short limbs). Compound het variants in the TRAPPC12 gene were identified in 2 affected fetuses, which segregated with the disorder.

- PMID: 28777934 (2017) - Three individuals from two unrelated families with severe GDD, seizures, hearing loss, microcephaly, and structural brain abnormalities including ventriculomegaly, pons hypoplasia, agenesis of the corpus callosum and brain atrophy. In family 1 (consanguineous), five previous pregnancies ended in spontaneous abortions and a sixth was terminated as a result of multiple anomalies; however, genetic analysis was not performed on these cases. In family 2, ultrasound and fetal MRI revealed agenesis of the corpus callosum but no other abnormal imaging findings in one individual.

Exome sequencing revealed different biallelic TRAPPC12 variants in both families. Patient-derived fibroblasts showed fragmentation of the Golgi, abnormal Golgi trafficking and delays in mitosis.
Created: 20 Jan 2021, 12:32 p.m. | Last Modified: 20 Jan 2021, 12:32 p.m.

Panel Version: 1.158

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Hydrocephaly; Encephalopathy, progressive, early-onset, with brain atrophy and spasticity, OMIM:617669; Early-onset progressive encephalopathy-hearing loss-pons hypoplasia-brain atrophy syndrome, MONDO:0044696

Publications

Created: 20 Jan 2021, 12:32 p.m.
Last Modified: 3 Mar 2022, 4:35 p.m.
Panel version: 1.836

Rhiannon Mellis (Great Ormond Street Hospital)

Green List (high evidence)

Two fetuses in one family with hydrocephaly and compound het variants. PMID: 32347653 (Gass et al 2020)

This gene is already green on other panels (Intellectual disability; Severe paediatric disorders). Here adding evidence for a fetally relevant phenotype.
Created: 30 Oct 2020, 2:30 p.m. | Last Modified: 30 Oct 2020, 2:30 p.m.

Panel Version: 1.108

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Hydrocephaly

Publications

32347653

Created: 30 Oct 2020, 2:30 p.m.
Last Modified: 30 Oct 2020, 2:30 p.m.
Panel version: 1.108

Rebecca Foulger (Genomics England curator)

I don't know

DDG2P rating in original PAGE list: Probable for Progressive Childhood Encephalopathy and Golgi Dysfunction
Created: 11 Dec 2018, 9:05 a.m.

Polygenic tag added because MOI was listed as 'Digenic' in original PAGE file.
Created: 8 Nov 2018, 4:57 p.m.

Created: 8 Nov 2018, 4:57 p.m.

Panel version: 0.9

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

Expert Review Green
PAGE DD-Gene2Phenotype

Phenotypes

Hydrocephaly
Encephalopathy, progressive, early-onset, with brain atrophy and spasticity, OMIM:617669
Early-onset progressive encephalopathy-hearing loss-pons hypoplasia-brain atrophy syndrome, MONDO:0044696

OMIM

614139

Clinvar variants

Variants in TRAPPC12

Penetrance

None

Publications

Panels with this gene