Segmental overgrowth disorders - Deep sequencing
Gene: AKT2Comment on list classification: At least three unrelated families reported with the same activating mosaic c.49G>A (p.E17K) variant in the AKT2 gene. Mild asymmetric overgrowth was seen in 2/3 cases. Sibs from the third family showed early overgrowth but no signs of body asymmetry. Overall the evidence is borderline amber/green. However, as this gene has been expert reviewed as green by Tom Cullup (GOSH) and is likely to be diagnostically relevant, recommending AKT2 is promoted to green status at the next GMS panel update.Created: 9 Aug 2023, 10:50 a.m. | Last Modified: 9 Aug 2023, 10:50 a.m.
Panel Version: 3.12
Hot-spot variant Glu17Lys reported multiple times de novo, at least twice mosaic (21979934; 24285683)Created: 3 May 2023, 3:46 p.m. | Last Modified: 3 May 2023, 3:46 p.m.
Panel Version: 3.5
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
hypoinsulinemic hypoglycemia with hemihypertrophy (HIHGHH) (MIM 240900)
Publications
Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Comment on list classification: After consultation with Genomics England clinical team who identified AKT2 in the review paper PMID:28502730 – "4 cases summarised, they all have the same missense variant, and I can’t see if any work has been done re mechanism e.g. gain of function". Advised rating as Amber.Created: 11 Dec 2019, 11:04 a.m. | Last Modified: 11 Dec 2019, 11:04 a.m.
Panel Version: 1.9
Gene: akt2 has been classified as Amber List (Moderate Evidence).
Publications for gene: AKT2 were set to 28502730
Mode of pathogenicity for gene: AKT2 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Tag Q3_23_promote_green tag was added to gene: AKT2. Tag Q3_23_NHS_review tag was added to gene: AKT2. Tag recurrent-variant tag was added to gene: AKT2.
Phenotypes for gene: AKT2 were changed from Hypoinsulinemic hypoglycemia with hemihypertrophy,240900; Hypoinsulinemic hypoglycemia with hemihypertrophy; HIHGHH; Hypoinsulinemic hypoglycemia with hemihypertrophy, 240900 to Hypoinsulinemic hypoglycemia with hemihypertrophy, OMIM:240900; Hypoinsulinemic hypoglycemia and body hemihypertrophy, MONDO:0009416
Publications for gene: AKT2 were set to
Gene: akt2 has been classified as Amber List (Moderate Evidence).
28 November 2016: Reviews were assessed, and panel was revised according to expert review and additional curation.
AKT2 was added to Regional overgrowth disorderspanel. Source: Other Model of inheritance for gene AKT2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
AKT2 was added to Regional overgrowth disorderspanel. Sources: Radboud University Medical Center, Nijmegen
AKT2 was created by rfoulger