Genes in panel
Regions in panel
Prev Next

Intellectual disability

Gene: DPH2

Amber List (moderate evidence)

DPH2 (DPH2 homolog)
EnsemblGeneIds (GRCh38): ENSG00000132768
EnsemblGeneIds (GRCh37): ENSG00000132768
OMIM: 603456, Gene2Phenotype
DPH2 is in 1 panel

2 reviews

Arina Puzriakova (Genomics England Curator)

Comment on list classification: New gene added by Zornitza Stark. Currently not associated with any phenotype in OMIM or Gene2Phenotype.

At least 2 unrelated families with biallelic variants in this gene. Phenotypes included DD with expressive language delays in the 19-month-old male in PMID: 32576952 (2020); and intellectual disability in both sibs in PMID: 27421267 (2016), albeit within the mild range (Stanford-Binet scale IQ = 58 and 68, respectively). However in the latter case, KALRN was proposed as the causative gene at the time of publication, as scarce data was known for the DPH2 gene.

Additional cases would help corroborate this gene-disease association and so rating Amber, awaiting further cases/clinical evidence.
Created: 22 Jan 2021, 12:13 p.m. | Last Modified: 22 Jan 2021, 12:13 p.m.
Panel Version: 3.721

Zornitza Stark (Australian Genomics)

I don't know

One 19 month old reported (PMID:32576952) with biallelic (one missense, one nonsense) variants in DPH2, with phenotype similar to DPH1 deficiency (gross motor delay, not walking, fine motor and expressive language delays, macrocephaly)

Another family (sibs) was previously reported with biallelic nonsense variants (PMID:27421267) with a comparable phenotype, this family also has biallelic variants in KALRN and the authors thought those variants more likely causative. Patients had ID and microcephaly (in contrast to the 19 month old above).

In vitro functional assays support reduced diphthamide synthesis activity for the variants identified in PMID:32576952.
Sources: Literature
Created: 7 Jan 2021, 9:25 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Diphthamide-deficiency syndrome



Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
  • Expert Review Amber
  • Diphthamide-deficiency syndrome
Clinvar variants
Variants in DPH2
Panels with this gene

History Filter Activity

22 Jan 2021, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: dph2 has been classified as Amber List (Moderate Evidence).

7 Jan 2021, Gel status: 0

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

Zornitza Stark (Australian Genomics)

gene: DPH2 was added gene: DPH2 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: DPH2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DPH2 were set to 32576952; 27421267 Phenotypes for gene: DPH2 were set to Diphthamide-deficiency syndrome Review for gene: DPH2 was set to AMBER