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Intellectual disability

Gene: NSD2

Green List (high evidence)

NSD2 (nuclear receptor binding SET domain protein 2)
EnsemblGeneIds (GRCh38): ENSG00000109685
EnsemblGeneIds (GRCh37): ENSG00000109685
OMIM: 602952, Gene2Phenotype
NSD2 is in 2 panels

2 reviews

Ivone Leong (Genomics England Curator)

Comment on list classification: New gene added by external expert and reviewed by curation team: Sufficient evidence has been provided by the external expert review for this gene to be rated green. NSD2 is not associated with any phenotypes on OMIM or Gene2Phenotypes.
Created: 22 Feb 2019, 11:08 a.m.

Konstantinos Varvagiannis (Other)

Green List (high evidence)

PMID: 29892088 reports on 2 individuals with de novo SNVs affecting NSD2 (WHSC1). Both individuals presented with pre- and postnatal growth retardation, hypotonia, developmental delay / intellectual disability, as well as microcephaly. The authors suggest partial overlap with the phenotype of Wolf-Hirschhorn syndrome (WHS). Seizures are not part of the phenotype.The first subject had a splice site mutation while the second individual had a stopgain variant (affecting the PWWP domain).

PMID: 29760529 describes a further patient with de novo nonsense mutation in NSD2. The boy was evaluated for probable growth delay ("low physical development"), hypotonia, psychomotor delay and microcephaly. The variant affected the SET domain.

Three individuals with de novo likely loss-of-function (two frameshift and one stop gained) variants in Decipher [ https://decipher.sanger.ac.uk/search?q=NSD2#research-variants/results ].

A further patient with de novo frameshift mutation in NSD2 and a phenotype overlapping WHS reported in ClinVar [ https://www.ncbi.nlm.nih.gov/clinvar/variation/547999/ ]

PMID: 29884796 (Zollino M and Doronzio PN) comments that NSD2 (WHSC1) is a neurodevelopmental gene with a role in growth delay, intellectual disability and dysmorphic facial features.

PMID: 30244530 describes patients with 4p16.3 microdeletions spanning (exclusively) NSD2 and reviews the literature on patients with small microdeletions reported to date. All relevant individuals present with developmental delay and (rather mild) intellectual disability apart from other characteristics such as microcephaly, growth retardation and some facial features also observed in WHS.

In Decipher one individual (286913) with a single CNV spanning exclusively NSD2 presenting with IUGR, failure to thrive, feeding difficulties, postnatal microcephaly, hypotonia, developmental delay as well as possibly relevant facial features.

The gene is included in ID gene panels offered by various labs (either as NSD2 or WHSC1).

As a result it can be considered for inclusion in the panel as green.
Sources: Literature, Expert Review
Created: 11 Oct 2018, 11:35 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Intrauterine growth retardation; Growth delay; Microcephaly; Muscular hypotonia; Neurodevelopmental delay; Intellectual disability

Publications

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

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
Phenotypes
  • Intrauterine growth retardation
  • Growth delay
  • Microcephaly
  • Muscular hypotonia
  • Neurodevelopmental delay
  • Intellectual disability
  • No OMIM number
OMIM
602952
Clinvar variants
Variants in NSD2
Penetrance
unknown
Publications
Panels with this gene

History Filter Activity

22 Feb 2019, Gel status: 3

Entity classified by Genomics England curator

Ivone Leong (Genomics England Curator)

Gene: nsd2 has been classified as Green List (High Evidence).

22 Feb 2019, Gel status: 0

Set Phenotypes

Ivone Leong (Genomics England Curator)

Phenotypes for gene: NSD2 were changed from Intrauterine growth retardation; Growth delay; Microcephaly; Muscular hypotonia; Neurodevelopmental delay; Intellectual disability to Intrauterine growth retardation; Growth delay; Microcephaly; Muscular hypotonia; Neurodevelopmental delay; Intellectual disability; No OMIM number

11 Oct 2018, Gel status: 0

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

Konstantinos Varvagiannis (Other)

gene: NSD2 was added gene: NSD2 was added to Intellectual disability. Sources: Literature,Expert Review Mode of inheritance for gene: NSD2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: NSD2 were set to 29892088; 29760529; 29884796; 30244530 Phenotypes for gene: NSD2 were set to Intrauterine growth retardation; Growth delay; Microcephaly; Muscular hypotonia; Neurodevelopmental delay; Intellectual disability Penetrance for gene: NSD2 were set to unknown Review for gene: NSD2 was set to GREEN gene: NSD2 was marked as current diagnostic