Intellectual disability
Gene: NUDT2

NUDT2 (nudix hydrolase 2)
EnsemblGeneIds (GRCh38): ENSG00000164978
EnsemblGeneIds (GRCh37): ENSG00000164978
OMIM: 602852, Gene2Phenotype
NUDT2 is in 4 panels

5 reviews

Sarah Leigh (Genomics England Curator)

The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Created: 9 Mar 2022, 3:40 p.m. | Last Modified: 9 Mar 2022, 3:40 p.m.

Panel Version: 3.1510

Created: 9 Mar 2022, 3:40 p.m.
Last Modified: 9 Mar 2022, 3:40 p.m.
Panel version: 3.1510

Arina Puzriakova (Genomics England Curator)

Comment on list classification: This gene should be promoted to Green at the next GMS panel update (added 'for-review' tag). There are now at least 2 biallelic variants reported in 6 families - 3 of which present GDD and ID, while the remaining had delay but borderline intelligence.
Created: 3 Nov 2020, 2:03 p.m. | Last Modified: 3 Nov 2020, 2:03 p.m.

Panel Version: 3.510

Removed 'founder-effect' tag, as the recent publication (PMID: 33058507) identified by Zornitza Stark (Australian Genomics) provides evidence of additional pathogenic variants in the NUDT2 gene
Created: 3 Nov 2020, 1:36 p.m. | Last Modified: 3 Nov 2020, 1:36 p.m.

Panel Version: 3.507

Created: 3 Nov 2020, 1:36 p.m.
Last Modified: 3 Nov 2020, 1:36 p.m.
Panel version: 3.507

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Three individuals from two additional families reported with a different homozygous variant and ID/polyneuropathy phenotype.
Created: 2 Nov 2020, 9:49 a.m. | Last Modified: 2 Nov 2020, 9:49 a.m.

Panel Version: 3.500

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Muscular hypotonia; Global developmental delay; Intellectual disability; Polyneuropathy

Publications

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

Created: 2 Nov 2020, 9:49 a.m.
Last Modified: 2 Nov 2020, 9:49 a.m.
Panel version: 3.500

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.

Created: 22 Feb 2019, 3:15 p.m.

Panel version: 2.737

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

Created: 21 Nov 2018, 1:41 a.m.

Panel version: 2.551

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

Expert Review Green

Phenotypes

Muscular hypotonia
Global developmental delay
Intellectual disability
Polyneuropathy
no OMIM number

OMIM

602852

Clinvar variants

Variants in NUDT2

Penetrance

Complete

Publications

Panels with this gene