Intellectual disability
Gene: VPS53

VPS53 (VPS53, GARP complex subunit)
EnsemblGeneIds (GRCh38): ENSG00000141252
EnsemblGeneIds (GRCh37): ENSG00000141252
OMIM: 615850, Gene2Phenotype
VPS53 is in 9 panels

2 reviews

Louise Daugherty (Genomics England Curator)

Comment on list classification: After internal clinical review it was decided that this gene could be rated Green. Even though there is a founder effect in this population, there is further evidence for it being the gene of interest by the fact that there is more than one variant identified. There are 4 unrelated families and two variants.
Created: 20 Jul 2018, 11:49 a.m.

Comment on phenotypes: added phenotypes to support gene on ID panel . All 10 patients of the four apparently unrelated non-consanguineous Jewish Moroccan families had profound mental retardation, gaining practically no developmental milestones except visual tracking and smiling.
Created: 16 Jul 2018, 1:59 p.m.

Comment on list classification: New Amber gene added by external expert review, publications support gene-disease association and noted from literature and review this is a founder-effect gene. Referred to internal clinical to consider rating Green review due to presence of missense and splice site variants
Created: 16 Jul 2018, 1:51 p.m.

added founder-effect tag
Created: 16 Jul 2018, 1:46 p.m.

It was noted by Feinstein et al. (2014) that the variants segregated with the disorder in the families. The Q695R substitution occured at a highly conserved residue in the second helix of the surface of the C terminus. Study of patient lymphocytes suggested that the splice site mutation was either subject to nonsense-mediated mRNA decay or resulted in a truncated protein. Of Jewish Moroccan controls tested, 2 of 143 carried the missense mutation and 2 of 156 carried the splice site mutation, yielding a carrier frequency of 1 in 37 for each of the mutations in this population, consistent with a founder effect
Created: 16 Jul 2018, 1:44 p.m.

Comment on publications: PMID:24577744. In 10 affected individuals from 4 nonconsanguineous families of Jewish Moroccan descent with pontocerebellar hypoplasia type 2E (PCH2E; 615851), Feinstein et al. (2014) identified two compound heterozygous mutations in the VPS53 gene. NM_001128159.2(VPS53):c.2084A>G (p.Gln695Arg) and NM_001128159.2(VPS53):c.1556+5G>A
Created: 16 Jul 2018, 1:36 p.m.

Comment on phenotypes: added omim MIMid and Orphanet phenotype
Created: 16 Jul 2018, 1:31 p.m.

Created: 16 Jul 2018, 1:31 p.m.

Panel version: 2.155

Zornitza Stark (Australian Genomics)

I don't know

10 individuals from 4 families reported in the literature with bi-allelic variants, but ?founder effect. Consider inclusion as Amber if not Green.
Created: 22 Jun 2018, 3:05 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Pontocerebellar hypoplasia, type 2E

Publications

24577744

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

Created: 22 Jun 2018, 3:05 p.m.

Panel version: 2.109

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

Victorian Clinical Genetics Services
Expert Review Green

Phenotypes

Pontocerebellar hypoplasia, type 2E, 615851
Progressive cerebello-cerebral atrophy
intellectual disability
developmental delay

Tags

founder-effect

OMIM

615850

Clinvar variants

Variants in VPS53

Penetrance

None

Publications

Panels with this gene