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Intellectual disability

Gene: NUDT2

Amber List (moderate evidence)

NUDT2 (nudix hydrolase 2)
EnsemblGeneIds (GRCh38): ENSG00000164978
EnsemblGeneIds (GRCh37): ENSG00000164978
OMIM: 602852, Gene2Phenotype
NUDT2 is in 1 panel

2 reviews

Ivone Leong (Genomics England Curator)

Comment on list classification: New gene added by external expert and reviewed by curation team. NUDT2 has been given an amber gene rating (as all reported cases are from the same geographical region) based on the evidence provided by Konstantinos Varvagiannis.
Created: 22 Feb 2019, 3:15 p.m.

Konstantinos Varvagiannis (Other)

I don't know

PMID: 27431290 reports briefly on 2 sibs from a consanguineous Saudi family, as part of a cohort of 337 patients investigated for intellectual disability. Both were homozygous for a nonsense NUDT2 mutation [NM_001161.4:c.34C>T or p.Arg12Ter / rs148119952]. The common features included hypotonia, global developmental delay (first words at 2.5 years, sitting at 2-2.5 years,walking achieved by 4 years - valid for both sibs) and intellectual disability. No other candidate variants were found in the exome.

PMID: 30059600 is a further report on 5 individuals from 3 consanguineous families from Saudi Arabia. All presented with low birth weight and height, poor suck, hypotonia, motor and language delay and borderline intelligence. All patients were homozygous for the same nonsense variant (Arg12Ter) which seems to be a founder mutation in Saudi Arabia.

As truncating NUDT2 variants have a combined allele frequency of 0.02% in gnomAD (no homozygotes in the database) the authors comment that most of the other LoF variants observed are in the second - and last - exon of the gene (thus probably escaping NMD) and downstream of its catalytic domain.

As a result this gene can be considered for inclusion in the ID panel probably as amber (single founder mutation - the degree of intellectual disability appears to be more severe in the first report but borderline in the subsequent) or green.
Sources: Literature, Expert Review
Created: 21 Nov 2018, 1:41 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Muscular hypotonia; Global developmental delay; Intellectual disability

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
Phenotypes
  • Muscular hypotonia
  • Global developmental delay
  • Intellectual disability
  • no OMIM number
Tags
founder-effect
OMIM
602852
Clinvar variants
Variants in NUDT2
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

22 Feb 2019, Gel status: 2

Entity classified by Genomics England curator

Ivone Leong (Genomics England Curator)

Gene: nudt2 has been classified as Amber List (Moderate Evidence).

22 Feb 2019, Gel status: 0

Added Tag

Ivone Leong (Genomics England Curator)

Tag founder-effect tag was added to gene: NUDT2.

22 Feb 2019, Gel status: 0

Set Phenotypes

Ivone Leong (Genomics England Curator)

Phenotypes for gene: NUDT2 were changed from Muscular hypotonia; Global developmental delay; Intellectual disability to Muscular hypotonia; Global developmental delay; Intellectual disability; no OMIM number

21 Nov 2018, Gel status: 0

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

Konstantinos Varvagiannis (Other)

gene: NUDT2 was added gene: NUDT2 was added to Intellectual disability. Sources: Literature,Expert Review Mode of inheritance for gene: NUDT2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NUDT2 were set to 27431290; 30059600 Phenotypes for gene: NUDT2 were set to Muscular hypotonia; Global developmental delay; Intellectual disability Penetrance for gene: NUDT2 were set to Complete Review for gene: NUDT2 was set to AMBER