Intellectual disability
Gene: NRXN2

NRXN2 (neurexin 2)
EnsemblGeneIds (GRCh38): ENSG00000110076
EnsemblGeneIds (GRCh37): ENSG00000110076
OMIM: 600566, Gene2Phenotype
NRXN2 is in 3 panels

5 reviews

Arina Puzriakova (Genomics England Curator)

Following discussion with the clinical team, this gene has been demoted from Amber to Red, in accordance with the external review by Zornitza Stark
Created: 17 Aug 2020, 10:09 a.m. | Last Modified: 17 Aug 2020, 10:09 a.m.

Panel Version: 3.253

Created: 17 Aug 2020, 10:09 a.m.
Last Modified: 17 Aug 2020, 10:09 a.m.
Panel version: 3.253

Louise Daugherty (Genomics England Curator)

I don't know

Comment on list classification: Changed from Green to Amber. After internal clinical review- Autism without moderate (or greater) learning difficulty is not a relevant phenotype for this panel. The penetrance is unclear and the evidence to date is from CNVs.
Created: 29 Aug 2018, 2:52 p.m.

Added tag for CNV and autism spectrum
Created: 29 Aug 2018, 2:35 p.m.

Past onto internal clinical team for further review and consideration to downgrade rating.
Created: 8 Aug 2018, 1:36 p.m.

Comment on publications: NRXN2 is specifically associated to ASD (PMID:21424692; 26164757, 29654904). Gauthier and colleagues sequenced all of the exons and splice junctions of NRXN1–3 in 379 subjects affected by ASD, schizophrenia, or non-syndromic intellectual disability (NSID). Two patients with 11q13.1 deletion involving neurexin 2 (NRXN2) have been reported (PMID:21600320, 26164757). Both patients exhibited autistic features, which supported the role of NRXN2 in autism pathogenicity. It is currently unknown whether heterozygous deletion of NRXN2 is of high penetrance or if it is sufficient to result in autism behaviours. More recently PMID: 29654904 Yuan H et al., (2018) reported a third case of a 2-year-9-month old boy with developmental delay, short stature, significant language delay and other congenital anomalies. In contrast to previously reported cases, the boy did not present with autistic behaviors and did not meet the clinical diagnosis of autism. All three patients shared similar deleted intervals and had similar clinical features except for autistic behaviors. This study suggested that NRXN2 gene had incomplete penetrance for autistic behavioral phenotype.
Created: 8 Aug 2018, 12:58 p.m.

Created: 8 Aug 2018, 12:58 p.m.

Panel version: 2.393

Zornitza Stark (Australian Genomics)

Red List (low evidence)

One individual reported with autism and a paternally inherited variant in this gene, father had a language disorder. Another infant reported with severe EE and a maternally inherited variants in NRXN1 and a paternally inherited variant in NRXN2. Some animal data.
Created: 6 Mar 2020, 3:59 a.m. | Last Modified: 6 Mar 2020, 3:59 a.m.

Panel Version: 3.3

Can't find published evidence
Created: 19 Jun 2018, 3:44 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Autism

Publications

Created: 19 Jun 2018, 3:44 p.m.

Panel version: 3.3

Caroline Wright (Sanger)

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
AUTISM

Publications

Created: 5 Nov 2017, 2:42 a.m.

Panel version: 0

Lu Raymond (university of cambridge )

Green List (high evidence)

Created: 23 Feb 2016, 10:52 a.m.

Panel version: 0.306

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Sources

Expert Review Red

Phenotypes

autism spectrum disorder
intellectual disability

Tags

cnv Autism Spectrum Disorder

OMIM

600566

Clinvar variants

Variants in NRXN2

Penetrance

Complete

Publications

Panels with this gene

History Filter Activity

12 Oct 2020, Gel status: 1

Added New Source, Status Update

Arina Puzriakova (Genomics England Curator)

Source Expert Review Red was added to NRXN2. Rating Changed from Amber List (moderate evidence) to Red List (low evidence)

29 Aug 2018, Gel status: 2