Iron metabolism disorders

Gene: ALAS2

Green List (high evidence)

ALAS2 (5'-aminolevulinate synthase 2)
EnsemblGeneIds (GRCh38): ENSG00000158578
EnsemblGeneIds (GRCh37): ENSG00000158578
OMIM: 301300, Gene2Phenotype
ALAS2 is in 16 panels

4 reviews

PATRICIA BIGNELL (Oxford Hospitals NHS Foundation Trust)

Green List (high evidence)

I had a discussion with Cambridge and Dr WJH Griffiths to see what he recommends for patients with iron overload; advice was to include SLC25A38, GLRX5, ALAS2 and ABCB7. We have found 8 patients with Iron overload that have a variant in the above genes.
Created: 28 May 2019, 1:11 p.m.
PRESENT WITH IRON OVERLOAD
Created: 28 May 2019, 1:11 p.m.

Frances Smith (King's College Hospital)

Green List (high evidence)

Louise Daugherty (Genomics England Curator)

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, 3:16 p.m. | Last Modified: 22 Jul 2019, 3:16 p.m.
Panel Version: 0.51
Follow up email correspondence with Patricia Bignell 13th March (webex 8.03.19 WWMGLH comments v1.doc), on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group, suggested rating Green
Created: 28 May 2019, 2:08 p.m.
New review/rating by Frances Smith, Viapath Kings College Hospital (Curation_Template_GMS_Haem_FS_updated_reviews_20190425.xlsx) on behalf of London South GLH for the GMS Haematology specialist test group. Gene rated as Green.
Created: 4 May 2019, 8:55 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: ALAS2; Suggested initial gene rating: Green List (high evidence); Are variants in this gene part of your current diagnostic practice? Yes; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Phenotypes: 300751 Anemia, sideroblastic, 1; 300752 Protoporphyria, erythropoietic, X-linked; PMID(s): 30401706; 30098397; 24003969
Created: 5 Feb 2019, 5:51 p.m.

Carl Fratter (Oxford University Hospitals NHS Trust)

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.
March 2019 Additional comments
Present with moderate to severe iron overload with mild-severe anaemia and this is the phenotype the clinicians pick up through the haematology/biochemistry screening
Created: 5 Feb 2019, 5:50 p.m.

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

Details

Mode of Inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Sources
  • Expert Review Green
  • London South GLH
  • NHS GMS
  • Wessex and West Midlands GLH
Phenotypes
  • Protoporphyria, erythropoietic, X-linked OMIM:300752
  • Anemia, sideroblastic, 1 OMIM:300751
  • X-linked erythropoietic protoporphyria MONDO:0010420
  • X-linked sideroblastic anemia 1 MONDO:0020721
OMIM
301300
Clinvar variants
Variants in ALAS2
Penetrance
None
Publications
Panels with this gene

History Filter Activity

2 Mar 2021, Gel status: 3

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: ALAS2 were changed from 300752 Protoporphyria, erythropoietic, X-linked; 300751 Anemia, sideroblastic, 1; Sideroblastic anaemia - increased serum ferritin to Protoporphyria, erythropoietic, X-linked OMIM:300752; Anemia, sideroblastic, 1 OMIM:300751; X-linked erythropoietic protoporphyria MONDO:0010420; X-linked sideroblastic anemia 1 MONDO:0020721

22 Jul 2019, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: alas2 has been classified as Green List (High Evidence).

4 May 2019, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

Source London South GLH was added to ALAS2.

4 May 2019, Gel status: 4

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: ALAS2 were set to 30401706; 24003969; 30098397

4 May 2019, Gel status: 4

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: ALAS2 were changed from 300752 Protoporphyria, erythropoietic, X-linked; 300751 Anemia, sideroblastic, 1 to 300752 Protoporphyria, erythropoietic, X-linked; 300751 Anemia, sideroblastic, 1; Sideroblastic anaemia - increased serum ferritin

5 Feb 2019, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to ALAS2.

5 Feb 2019, Gel status: 3

Added New Source, Set mode of inheritance, Set Phenotypes, Set publications, Status Update

Louise Daugherty (Genomics England Curator)

Source Expert Review Green was added to ALAS2. Mode of inheritance for gene ALAS2 was changed from to X-LINKED: hemizygous mutation in males, biallelic mutations in females Added phenotypes 300752 Protoporphyria, erythropoietic, X-linked; 300751 Anemia, sideroblastic, 1 for gene: ALAS2 Publications for gene ALAS2 were changed from to 30401706; 24003969; 30098397 Rating Changed from Red List (low evidence) to Green List (high evidence)

5 Feb 2019, Gel status: 1

Created, Added New Source, Set mode of inheritance

Louise Daugherty (Genomics England Curator)

gene: ALAS2 was added gene: ALAS2 was added to Iron metabolism disorders. Sources: Wessex and West Midlands GLH Mode of inheritance for gene: ALAS2 was set to