Bleeding and platelet disorders

Gene: PRKACG

Red List (low evidence)

Recommend Amber rating. Evidence for gene-phenotype association is limited to one family and functional work on patient CD34+ derived MKs. Further evidence in independent families and cellular or animal models required for considering this gene-disease association as clinically actionable. Tier 2 rating (Amber) curated by ISTH SSC Genomics in Thrombosis and Hemostasis Subcommittee.

Created: 31 Jan 2021, 12:47 p.m. | Last Modified: 31 Jan 2021, 12:47 p.m.

Panel Version: 1.19

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Macrothrombocytopenia

Publications

• PMID: 25061177

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

The rating of this gene has been updated following NHS Genomic Medicine Service approval. It was agreed that PRKACG should be Red.

Created: 4 Mar 2022, 9:41 a.m. | Last Modified: 4 Mar 2022, 9:42 a.m.

Panel Version: 1.33

Comment on list classification: Current Green gene rating based on GMS specialist test group consensus; however, note the recent review by Zornitza Stark (Australian Genomics) highlighting limited published evidence to support this gene-disease association. Based on literature, only sufficient for an Amber/Red rating. Will be flagged for review at the next GMS panel update (added 'for-review' tag).

Created: 14 Jan 2021, 10:47 a.m. | Last Modified: 14 Jan 2021, 10:47 a.m.

Panel Version: 1.14

Red List (low evidence)

Single family reported only. A heterozygous VOUS reported in another individual in PMID 30819905 together with several other VOUS in same individual.

Created: 16 Aug 2020, 3:26 a.m. | Last Modified: 16 Aug 2020, 3:26 a.m.

Panel Version: 1.6

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Bleeding disorder, platelet-type, 19, MIM# 616176

Publications

• 25061177
• 30819905

Green List (high evidence)

Gene rating submitted by Steve Keeney Molecular Diagnostics Centre Central Manchester NHS Foundation Trust January 2019 on behalf of North West GLH for the GMS Haematology specialist test group

Created: 18 Feb 2019, 11:23 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
616176 BLEEDING DISORDER, PLATELET-TYPE, 19; BDPLT19

Green List (high evidence)

Gene rating submitted by Mandy Nesbitt Sheffield Diagnostic Genetics Service, Sheffield Children's NHS Trust January 2019 on behalf of Yorkshire and North East GLH for the GMS Haematology specialist test group.

Created: 13 Feb 2019, 11:32 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
616176BLEEDING DISORDER, PLATELET-TYPE, 19; BDPLT19

Green List (high evidence)

Gene rating submitted by Mike Mitchell Viapath St. Thomas' Hospital January 2019 on behalf of London South GLH for the GMS Haematology specialist test group.

Created: 7 Feb 2019, 1:21 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
616176.BLEEDING DISORDER, PLATELET-TYPE, 19; BDPLT19

I don't know

Initial gene list (Consensus Genes for SPEC HAEM Panels 31.01.19 North West v1 FINAL.xlsx) collated by Steve Keeney Molecular Diagnostics Centre Central Manchester NHS Foundation Trust January 2019 on behalf of North West GLH for the GMS Haematology specialist test group. Gene Symbol submitted: PRKACG; Suggested initial gene rating: Green List (high evidence); Are variants in this gene part of your current diagnostic practice? No; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Phenotypes: 616176.BLEEDING DISORDER, PLATELET-TYPE, 19; BDPLT19; PMID(s): none submitted

Created: 18 Feb 2019, 11:28 a.m.

Initial gene list (Consensus Genes for Panels_Haem_SHEFFIELD-29.01.2019.xlsx) collated by Mandy Nesbitt Sheffield Diagnostic Genetics Service, Sheffield Children's NHS Trust January 2019 on behalf of Yorkshire and North East GLH for the GMS Haematology specialist test group. Gene Symbol submitted: PRKACG; Suggested intial gene rating: Green List (high evidence); Are variants in this gene part of your current diagnostic practice? No; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Phenotypes: 616176BLEEDING DISORDER, PLATELET-TYPE, 19; BDPLT19; PMID(s): none submitted

Created: 13 Feb 2019, 11:34 a.m.

Initial gene list (Consensus Genes for Panels_Bleeding and Thrombosis_South London.xlsx) collated by Mike Mitchell Viapath St. Thomas' Hospital January 2019 on behalf of London South GLH for the GMS Haematology specialist test group. Gene Symbol submitted: PRKACG; Suggested intial gene rating: Green List (high evidence); Are variants in this gene part of your current diagnostic practice? No; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Phenotypes: 616176.BLEEDING DISORDER, PLATELET-TYPE, 19; BDPLT19; PMID(s): none submitted

Created: 7 Feb 2019, 1:28 p.m.

Initial gene list (Consensus Genes for Panels 17.12.18_Haem_WWMGLH_v3.xlxs) collated by Carl Fratter Oxford Medical Genetics Laboratories January 2019 on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group. Gene Symbol submitted: PRKACG; Suggested intial gene rating: Green List (high evidence); Are variants in this gene as part of your current diagnostic practice? No; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Phenotypes: 616176 BLEEDING DISORDER, PLATELET-TYPE, 19; BDPLT19; PMID(s): 25061177

Created: 5 Feb 2019, 1:26 p.m.

Green List (high evidence)

Gene rating submitted by Carl Fratter Oxford Medical Genetics Laboratories January 2019 on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group.

Created: 5 Feb 2019, 11:19 a.m.