Mosaic skin disorders - deep sequencing

Gene: AKT3

Green List (high evidence)

AKT3 (AKT serine/threonine kinase 3)
EnsemblGeneIds (GRCh38): ENSG00000117020
EnsemblGeneIds (GRCh37): ENSG00000117020
OMIM: 611223, Gene2Phenotype
AKT3 is in 13 panels

4 reviews

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Created: 6 Dec 2024, 11:18 a.m. | Last Modified: 6 Dec 2024, 11:18 a.m.
Panel Version: 2.49

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Arina Puzriakova (Genomics England Curator)

Comment on list classification: Variants in this gene cause a spectrum of megalencephaly-related disorders, which in some cases can present as megalencephaly-capillary malformation syndrome (MCAP). Both somatic and germline variants have been reported. Vascular skin anomalies have been identified in at least 2 individuals with germline variants (PMIDs: 22729224; 23745724) and 5 individuals with somatic variants (PMIDs: 25722288; 28969385; 34237354; 36695285; 37395289) meaning that AKT3 can be promoted to green at the next GMS panel update.
Created: 9 Aug 2023, 1:32 p.m. | Last Modified: 9 Aug 2023, 1:32 p.m.
Panel Version: 2.20

Tom Cullup (Great Ormond Street Hospital)

Green List (high evidence)

Previously not included in R327 (R110 only), but is a differential in patients referred for R327 only.
Created: 3 May 2023, 1:05 p.m. | Last Modified: 3 May 2023, 1:05 p.m.
Panel Version: 2.1

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome-2 (MPPH2) (615937)

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

Rebecca Foulger (Genomics England curator)

Green List (high evidence)

This gene was part of an initial gene list collated by Thomas Cullup, GOSH and Veronica Kinsler, UCL, 25.Jan.2019 on behalf of the GMS Skin Specialist Test Group. Gene Symbol submitted: AKT3; Suggested initial gene rating: Green; Evidence for inclusion: none provided; Evidence for exclusion: none provided; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none provided.
Created: 31 Jan 2019, 2:50 p.m.

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • London North GLH
  • NHS GMS
Phenotypes
  • Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2, OMIM:615937
OMIM
611223
Clinvar variants
Variants in AKT3
Penetrance
None
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
Panels with this gene

History Filter Activity

6 Dec 2024, Gel status: 3

Removed Tag, Removed Tag

Achchuthan Shanmugasundram (Genomics England Curator)

Tag Q3_23_promote_green was removed from gene: AKT3. Tag Q3_23_NHS_review was removed from gene: AKT3.

6 Dec 2024, Gel status: 3

Added New Source, Status Update

Achchuthan Shanmugasundram (Genomics England Curator)

Source Expert Review Green was added to AKT3. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

9 Aug 2023, Gel status: 2

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: AKT3 were changed from Overgrowth syndrome (not always mosaic in this case) to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2, OMIM:615937

9 Aug 2023, Gel status: 2

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: AKT3 were set to

9 Aug 2023, Gel status: 2

Set mode of pathogenicity

Arina Puzriakova (Genomics England Curator)

Mode of pathogenicity for gene: AKT3 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

9 Aug 2023, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: akt3 has been classified as Amber List (Moderate Evidence).

9 Aug 2023, Gel status: 0

Removed Tag, Added Tag, Added Tag

Arina Puzriakova (Genomics England Curator)

Tag curated_removed was removed from gene: AKT3. Tag Q3_23_promote_green tag was added to gene: AKT3. Tag Q3_23_NHS_review tag was added to gene: AKT3.

26 Feb 2021, Gel status: 0

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag curated_removed tag was added to gene: AKT3.

5 Dec 2019, Gel status: 0

Added New Source, Status Update

Catherine Snow (Genomics England)

Source Expert Review Removed was added to AKT3. Rating Changed from Green List (high evidence) to No List (delete)

18 Feb 2019, Gel status: 4

Added New Source

Rebecca Foulger (Genomics England curator)

Source London North GLH was added to AKT3.

31 Jan 2019, Gel status: 4

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

Rebecca Foulger (Genomics England curator)

gene: AKT3 was added gene: AKT3 was added to Mosaic skin disorders - deep sequencing. Sources: Expert Review Green,NHS GMS Mode of inheritance for gene: AKT3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: AKT3 were set to Overgrowth syndrome (not always mosaic in this case)