Intellectual disability
Gene: RNU2-2P

RNU2-2P (RNA, U2 small nuclear 2, pseudogene)
EnsemblGeneIds (GRCh38): ENSG00000222328
EnsemblGeneIds (GRCh37): ENSG00000222328
RNU2-2P is in 3 panels

2 reviews

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

Comment on list classification: There is sufficient evidence available for the association of this gene with ID and GDD. Hence, this gene can be promoted to green rating on the next GMS update.
Created: 14 Apr 2025, 10:31 a.m. | Last Modified: 14 Apr 2025, 10:31 a.m.

Panel Version: 8.242

The "new-gene-name" tag has been added as the official HGNC symbol for RNU2-2P is RNU2-2.

In addition, "locus-type-rna-small-nuclear" tag has been added to highlight the biotype for this gene.
Created: 14 Apr 2025, 10:29 a.m. | Last Modified: 14 Apr 2025, 10:29 a.m.

Panel Version: 8.241

PMID:40210679 reported nine individuals from 100,000 Genomes Project (100KGP) data in the National Genomic Research Library (NGRL) with a neurodevelopmental disorder and with recurrent de novo single-nucleotide variants at nucleotide positions 4 and 35 of RNU2-2 (n.4G>A & n.35A>G).

Monoallelic variants in this gene were also identified in 16 other cases with neurodevelopmental disorder from eight other rare disease collections. All but two of them were confirmed to have a de novo variant and 15 of them had one of the two variants reported from the 100KGP collection. There were no unaffected carriers of either variant. One case had a different variant at position 35 (35A>C).

Detailed clinical information was provided for 15 of these cases, and the disorder is characterised by intellectual disability (ID), autistic behaviour, microcephaly, hypotonia, epilepsy and hyperventilation. The phenotype typically manifests from 3 to 6 months of age but is progressive, frequently severe and accompanied by characteristic dysmorphic features. All cases had ID and global developmental delay, and displayed a severe and complex seizure phenotype.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Created: 14 Apr 2025, 10:15 a.m. | Last Modified: 14 Apr 2025, 10:23 a.m.

Panel Version: 8.238

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071

Publications

40210679

Created: 14 Apr 2025, 10:15 a.m.
Last Modified: 14 Apr 2025, 10:31 a.m.
Panel version: 8.241

Eleanor Williams (Genomics England Curator)

Red List (low evidence)

PRE-PRINT article https://doi.org/10.1101/2024.09.03.24312863

Greene et al 2024 - report 15 cases in which recurrent germline variants in RNU2-2P are found in patients with a severe neurodevelopmental disorder.

9 cases were from the 100,000 Genomes Project, all of which were annotated with Intellectual disability and displayed severe epilepsy usually from the first few months of life. Among these 9 two recurrent variants were found; n.4G>A and n.35A>G. Trio sequencing of 4/5 of the cases with n.4G>A and 3/4 of the cases with n.35A>G showed that the variants were de novo in all cases.

A variant with a different alternate allele at nucleotide 35, n.35A>T, was identified in
8 unaffected participants but further analysis suggests that this is a recurring somatic mosaic
variant.

A further 6 cases were identified in additional datasets of patients with neurodevelopmental abnormalities with de novo variants and no unaffected carriers of either variant; 4 cases had n.4G>A, 1 case had n.35A>G and 1 case had a different alternate allele, n.35A>C.

RNU2-2P is currently annotated as a pseudogene in Ensembl, but there is evidence that it is a transcribed gene from PMID.: 35288589
Sources: Literature
Created: 10 Sep 2024, 9:34 p.m.

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

Created: 10 Sep 2024, 9:34 p.m.

Panel version: 7.28

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Sources

Expert Review Amber
Literature

Phenotypes

neurodevelopmental disorder, MONDO:0700092
intellectual disability, MONDO:0001071

Tags

new-gene-name locus-type-rna-small-nuclear dd_review Q2_25_ promote_green

Clinvar variants

Variants in RNU2-2P

Penetrance

None

Publications

Panels with this gene

History Filter Activity

28 Jul 2025, Gel status: 2

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: RNU2-2P were set to 40210679; 40442284

28 Jul 2025, Gel status: 2

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: RNU2-2P were set to 40210679

14 Apr 2025, Gel status: 2