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Intellectual disability

Gene: DPYSL2

Amber List (moderate evidence)
DPYSL2 (dihydropyrimidinase like 2)
EnsemblGeneIds (GRCh38): ENSG00000092964
EnsemblGeneIds (GRCh37): ENSG00000092964
OMIM: 602463, Gene2Phenotype
DPYSL2 is in 1 panel

1 review

Achchuthan Shanmugasundram (Genomics England Curator)

I don't know

This gene should be rated AMBER, as it has been associated with intellectual disability (ID) from two unrelated cases displaying monoallelic variants in DPYSL2/ CRMP2, and supported by functional studies. However, the evidence is not sufficient for green rating as there are variants reported in other (but different) genes in the two patients.

PMID:35861646 reported two cases identified with heterozygous variants (patient1: c.1693C>T (p.Arg565Cys); patient 2: c.42C>A (p.Ser14Arg). These patients had overlapping phenotypes including dysmorphic features, severe global developmental delay and hypoplasia of the corpus callosum. In addition, patient 2 was bed-ridden and could not roll out and had a history of myoclonic seizures and status epilepticus.

It should be noted that patient 1 is compound heterozygous for 2 missense variants in the EFCAB5 gene and was hemizygous for a maternally inherited missense variant in the GPKOW gene and patient 2 had 1 de novo missense variant in the COBLL1 gene and was compound heterozygous for 2 missense variants in the POTEF gene. The severity of the phenotypes between the two cases differs significantly and the additional variants may have possibly contributed to this phenotype.

Brain-specific Crmp2 knockout mice display neuronal development deficits and behavioural impairments associated with hypoplasia of the corpus callosum. In addition, functional studies performed in zebrafish and cell lines that the CRMP2 variants lead to the loss-of-function of CRMP2 protein and can cause intellectual disability.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Created: 3 Mar 2023, 11 a.m. | Last Modified: 3 Mar 2023, 11:01 a.m.
Panel Version: 4.93

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
intellectual disability, MONDO:0001071; Aplasia/Hypoplasia of the corpus callosum, HP:0007370

Publications

Created: 3 Mar 2023, 11 a.m.
Last Modified: 3 Mar 2023, 11:01 a.m.
Panel version: 4.93

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Amber
  • Literature
Phenotypes
  • intellectual disability, MONDO:0001071
  • Aplasia/Hypoplasia of the corpus callosum, HP:0007370
OMIM
602463
Clinvar variants
Variants in DPYSL2
Penetrance
None
Publications
Panels with this gene

History Filter Activity

3 Mar 2023, Gel status: 2

Entity classified by Genomics England curator

Achchuthan Shanmugasundram (Genomics England Curator)

Gene: dpysl2 has been classified as Amber List (Moderate Evidence).

3 Mar 2023, Gel status: 2

Entity classified by Genomics England curator

Achchuthan Shanmugasundram (Genomics England Curator)

Gene: dpysl2 has been classified as Amber List (Moderate Evidence).

3 Mar 2023, Gel status: 1

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

Achchuthan Shanmugasundram (Genomics England Curator)

gene: DPYSL2 was added gene: DPYSL2 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: DPYSL2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: DPYSL2 were set to 27249678; 35861646 Phenotypes for gene: DPYSL2 were set to intellectual disability, MONDO:0001071; Aplasia/Hypoplasia of the corpus callosum, HP:0007370 Review for gene: DPYSL2 was set to AMBER