DEMO Diabetes neonatal onset

Gene: AGPAT2

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.

Green List (high evidence)

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.

Red List (low evidence)

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.

Comment on list classification: Gene add to the panel as green, due to expert review.

Created: 15 Jun 2016, 3:28 p.m.