Diabetes - neonatal onset

Gene: AGPAT2

Red List (low evidence)

AGPAT2 (1-acylglycerol-3-phosphate O-acyltransferase 2)
EnsemblGeneIds (GRCh38): ENSG00000169692
EnsemblGeneIds (GRCh37): ENSG00000169692
OMIM: 603100, Gene2Phenotype
AGPAT2 is in 11 panels

5 reviews

Ivone Leong (Genomics England Curator)

Red List (low evidence)

Submitted on behalf of Jayne Houghton (Royal Devon and Exeter Foundation Trust): "We have identified pathogenic variants in this gene in only two patients with neonatal diabetes from two different families. Therefore there is currently insufficient evidence for this being a neonatal diabetes gene (only 2 unrelated cases) and so this should not currently be changed to green using panelapp guidelines."
Created: 31 Jul 2019, 1:37 p.m. | Last Modified: 31 Jul 2019, 1:37 p.m.
Panel Version: 1.46
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: AGPAT2; 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 and lipodystrophy.
Created: 11 Jan 2019, 4:27 p.m.

Sian Ellard (University of Exeter Medical School)

Green List (high evidence)

Louise Daugherty (Genomics England Curator)

Red List (low evidence)

Clarification Note: these are not conflicting reviews, external reviewers are from same lab and on further review confirm that AGPAT2 is a candidate gene for the disorder, so should be Red.
Created: 31 May 2017, 9:20 a.m.

Elisa De Franco (University of Exeter Medical School)

Red List (low evidence)

Rebecca Foulger (Genomics England curator)

Comment when marking as ready: Marked AGPAT2 as ready: May 25th 2017.
Created: 25 May 2017, 9:14 a.m.
Comment on list classification: Updated rating from Grey to Red. AGPAT2 gene added (and rated green) by Sian Ellard during panel review. 1 case of neonatal diabetes reported in Poovazhagi et al., 2013. Elisa De-Franco (University of Exeter Medical School) reports that no AGPAT2 mutations have so far been found in the Exeter neonatal diabetes screen, so although it is a good candidate research gene, there is insufficient evidence to be included as a Green gene on this panel [personal communication, May 24th 2017].
Created: 25 May 2017, 9:13 a.m.
Poovazhagi et al., 2013 present a 42-day old male with a diagnosis of neonatal diabetes mellitus. One novel homozygous c.119 G>A (V67M) mutation was found in AGPAT2 (in addition to a synonymous variant c.411C>A). Parental samples could not be obtained for genetic analysis.
Created: 27 Apr 2017, 3:31 p.m.
Comment on mode of inheritance: Mode of inheritance supported by literature (Poovazhagi et al., 2013)
Created: 27 Apr 2017, 3:30 p.m.
Comment on publications: Poovazhagi et al., 2013, not listed in PubMed.
Created: 27 Apr 2017, 3:30 p.m.

History Filter Activity

3 Mar 2021, Gel status: 1

Set Phenotypes

Ivone Leong (Genomics England Curator)

Phenotypes for gene: AGPAT2 were changed from neonatal diabetes mellitus to neonatal diabetes mellitus, MONDO:0016391

3 Mar 2021, Gel status: 1

Set publications

Ivone Leong (Genomics England Curator)

Publications for gene: AGPAT2 were set to Poovazhagi et al., Int J Diabetes Dev Ctries (January–March 2013) 33(1):66–68, DOI 10.1007/s13410-012-0099-6

11 Jan 2019, Gel status: 1

Added New Source

Ivone Leong (Genomics England Curator)

Source NHS GMS was added to AGPAT2.

31 May 2017, Gel status: 1

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.

25 May 2017, Gel status: 1

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Red List (Low Evidence).

25 May 2017, Gel status: 1

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Red List (Low Evidence).

27 Apr 2017, Gel status: 0

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for AGPAT2 were set to neonatal diabetes mellitus

27 Apr 2017, Gel status: 0

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for AGPAT2 was changed to BIALLELIC, autosomal or pseudoautosomal

27 Apr 2017, Gel status: 0

Set publications

Rebecca Foulger (Genomics England curator)

Publications for AGPAT2 were set to Poovazhagi et al., Int J Diabetes Dev Ctries (January–March 2013) 33(1):66–68, DOI 10.1007/s13410-012-0099-6

18 Oct 2015, Gel status: 0

Added New Source

Sian Ellard (University of Exeter Medical School)

AGPAT2 was added to Neonatal diabetes diagnosed <6 monthspanel. Sources: Expert Review