Diabetes - neonatal onset

Gene: NKX2-2

Green List (high evidence)

NKX2-2 (NK2 homeobox 2)
EnsemblGeneIds (GRCh38): ENSG00000125820
EnsemblGeneIds (GRCh37): ENSG00000125820
OMIM: 604612, Gene2Phenotype
NKX2-2 is in 5 panels

4 reviews

Ivone Leong (Genomics England Curator)

Green List (high evidence)

Comment on phenotypes: Previous phenotypes:
Neonatal diabetes;Syndromic neonatal diabetes, with severe developmental delay, hypotonia, cortical blindness, hearing impairment
Created: 3 Mar 2021, 2:29 p.m. | Last Modified: 3 Mar 2021, 2:29 p.m.
Panel Version: 2.23
Initial gene list and info collated by Sian Ellard, University of Exeter Medical School, August 2018 on behalf of the GMS Endocrinology specialist test group. Gene Symbol submitted: NKX2-2; Suggested intial gene rating: Green; Evidence for inclusion: none given; Evidence for exclusion: none given; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none given; Phenotypes: Syndromic neonatal diabetes, with severe developmental delay, hypotonia, cortical blindness, hearing impairment.
Created: 11 Jan 2019, 4:27 p.m.

Sian Ellard (University of Exeter Medical School)

Green List (high evidence)

Elisa De Franco (University of Exeter Medical School)

We have identified no additional patients so far (only those reported in PMID:24411943).
Created: 29 May 2017, 8:34 a.m.

Rebecca Foulger (Genomics England curator)

Comment when marking as ready: Marked as ready: May 30th 2017.
Created: 30 May 2017, 9:53 a.m.
Comment on list classification: Updated rating from Red to Green after internal clinical discussion: Green expert review. 3 cases from 2 families, plus green on multiple diabetes PanelApp panels.
Created: 30 May 2017, 9:53 a.m.
Comment on mode of inheritance: Biallelic mode of inheritance supported by literature (PMID:24411943).
Created: 24 Apr 2017, 2 p.m.
PMID:24411943 (Flanagan et al., 2014) report 3 patients from 2 families with diabetes in infancy, and homozygous missense mutations in NKX2-2.
Created: 24 Apr 2017, 1:51 p.m.

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • NHS GMS
  • Expert Review Green
  • Eligibility statement prior genetic testing
  • UKGTN
Phenotypes
  • Neonatal diabetes mellitus, MONDO:0016391
  • Syndromic neonatal diabetes, with severe developmental delay, hypotonia, cortical blindness, hearing impairment
Tags
gene-checked
OMIM
604612
Clinvar variants
Variants in NKX2-2
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

10 May 2022, Gel status: 3

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag gene-checked tag was added to gene: NKX2-2.

3 Mar 2021, Gel status: 3

Set Phenotypes

Ivone Leong (Genomics England Curator)

Phenotypes for gene: NKX2-2 were changed from Neonatal diabetes; Syndromic neonatal diabetes, with severe developmental delay, hypotonia, cortical blindness, hearing impairment to Neonatal diabetes mellitus, MONDO:0016391; Syndromic neonatal diabetes, with severe developmental delay, hypotonia, cortical blindness, hearing impairment

15 Jul 2019, Gel status: 3

Set Phenotypes

Ivone Leong (Genomics England Curator)

Phenotypes for gene: NKX2-2 were changed from Neonatal diabetes to Neonatal diabetes; Syndromic neonatal diabetes, with severe developmental delay, hypotonia, cortical blindness, hearing impairment

11 Jan 2019, Gel status: 3

Added New Source, Status Update

Ivone Leong (Genomics England Curator)

Source NHS GMS was added to NKX2-2. Rating Changed from Green List (high evidence) to Green List (high evidence)

31 May 2017, Gel status: 4

panel promoted to version 1

Rebecca Foulger (Genomics England curator)

Promoted panel to Version 1: 31st May 2017. This panel is largely aligned with the Exeter Molecular Genetics Laboratory neonatal diabetes screen. Note that 8 genes feature on the Exeter 8-gene panel for patients with 'neonatal diabetes and autoimmune disease' (FOXP3, IL2RA, ITCH, LRBA, SIRT1, STAT1, STAT3 and STAT5). ITCH, SIRT1, STAT1 and STAT5A/B do not feature on this panel following correspondance with Elisa De-Franco (University of Exeter Medical School) that, at the time of curation, none of the patients with mutations in ITCH, SIRT1, STAT1 and STAT5b had diabetes diagnosed in the neonatal period, and therefore there is currently insufficient evidence to include these genes in this neonatal diabetes panel.

30 May 2017, Gel status: 4

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Green List (High Evidence).

30 May 2017, Gel status: 4

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Green List (High Evidence).

24 Apr 2017, Gel status: 1

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for NKX2-2 were set to Neonatal diabetes

24 Apr 2017, Gel status: 1

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for NKX2-2 was changed to BIALLELIC, autosomal or pseudoautosomal

24 Apr 2017, Gel status: 1

Set publications

Rebecca Foulger (Genomics England curator)

Publications for NKX2-2 were set to 24411943

17 Aug 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

NKX2-2 was added to Neonatal diabetes diagnosed <6 monthspanel. Sources: Eligibility statement prior genetic testing

17 Aug 2015, Gel status: 1

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene NKX2-2 was changed to BIALLELIC, autosomal or pseudoautosomal

17 Jul 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

NKX2-2 was added to Neonatal diabetes diagnosed <6 monthspanel. Sources: UKGTN