Cytopenia - NOT Fanconi anaemia

Gene: ACD

Comment on mode of inheritance: MOI changed from "BOTH monoallelic and biallelic, autosomal or pseudoautosomal" to "BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal" as the patient with AR inheritance had a more severe phenotype.

Created: 1 Jul 2021, 3:31 p.m. | Last Modified: 1 Jul 2021, 3:31 p.m.

Panel Version: 1.40

Comment on list classification: Only two families with DC who have variants in ACD have been reported since 2015 - one family with AD inheritance had only progressive bone marrow failure (PMID: 25205116) and one patient (patient B) with AR inheritance had a more severe phenotype (PMID: 25233904). However, this gene was rated Green on this and other panels following external clinical review - so this rating will be maintained at this time.

Created: 30 Jun 2021, 11:40 a.m. | Last Modified: 30 Jun 2021, 11:40 a.m.

Panel Version: 1.38

Red List (low evidence)

I can only find two families reported: one for each MOI.

Created: 19 Jun 2021, 2:02 a.m. | Last Modified: 19 Jun 2021, 2:02 a.m.

Panel Version: 1.37

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Dyskeratosis congenita, MIM# 616553

Publications

• 25205116
• 25233904

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, 2:55 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
616553 ?Dyskeratosis congenita 6 and 7

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: 14 Feb 2019, 5:39 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
616553 ?Dyskeratosis congenita 6 and 7

I don't know

Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. Gene was not submitted by all GLHs so needed further review by all the GLHs. All agreed that this gene should be in this panel and there is enough evidence to rate this gene Green.

Created: 22 Jul 2019, 1:20 p.m. | Last Modified: 22 Jul 2019, 1:22 p.m.

Panel Version: 0.77

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: ACD; Suggested initial gene rating: Green List (high evidence); Are variants in this gene part of your current diagnostic practice? No; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Phenotypes: 616553 ?Dyskeratosis congenita 6 and 7; PMID(s): 25205116; 25233904

Created: 18 Feb 2019, 2:57 p.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: ACD; Suggested initial gene rating: Green List (high evidence); Are variants in this gene part of your current diagnostic practice? No; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Phenotypes: 616553 ?Dyskeratosis congenita 6 and 7; PMID(s): none submitted

Created: 14 Feb 2019, 5:40 p.m.

Initial gene list (Consensus Genes for Haem Panels 17.12.18_KCH.xlsx) collated by Frances Smith Viapath Kings College Hospital February 2019 on behalf of London South GLH for the GMS Haematology specialist test group. Gene Symbol submitted: ACD; Suggested intial gene rating: Green List (high evidence); Are variants in this gene part of your current diagnostic practice? Yes; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Phenotypes: 616553 ?Dyskeratosis congenita 6 and 7; PMID(s): 25205116; 25233904

Created: 8 Feb 2019, 1:43 p.m.

Green List (high evidence)

Gene rating submitted by Frances Smith Viapath Kings College Hospital February 2019 on behalf of London South GLH for the GMS Haematology specialist test group.

Created: 8 Feb 2019, 1:36 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
616553 ?Dyskeratosis congenita 6 and 7

Variants in this GENE are reported as part of current diagnostic practice