Newborns additional phenotypes panel 1
Gene: ALAS2EnsemblGeneIds (GRCh38): ENSG00000158578
EnsemblGeneIds (GRCh37): ENSG00000158578
OMIM: 301300, Gene2Phenotype
ALAS2 is in 15 panels
3 reviews
Arina Puzriakova (Genomics England Curator)
Special Consideration: Females should be reported.
Additional Information: Report males and females.Created: 25 Sep 2024, 1:47 p.m. | Last Modified: 25 Sep 2024, 1:47 p.m.
Panel Version: 0.100
Special Consideration: Internal inclusion list onlyCreated: 25 Sep 2024, 1:46 p.m. | Last Modified: 25 Oct 2024, 10:36 a.m.
Panel Version: 0.100
Ivone Leong (Genomics England Curator)
Comment on mode of inheritance: MOI corrected from "X-LINKED: hemizygous mutation in males, biallelic mutations in females" to "X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)"Created: 6 Feb 2024, 8:53 a.m. | Last Modified: 6 Feb 2024, 8:53 a.m.
Panel Version: 0.61
Mafalda Gomes (Genomics England Curator)
The mechanism of pathogenicity is gain-of-function (GOF).Created: 1 Jun 2023, 2:40 p.m. | Last Modified: 1 Jun 2023, 2:40 p.m.
Panel Version: 0.29
ALAS2 curation results (clinicalgenome.org)Created: 1 Jun 2023, 12:22 p.m. | Last Modified: 1 Jun 2023, 12:22 p.m.
Panel Version: 0.26
All cases reported to date are due to a GoF variant in Exon 11Created: 1 Jun 2023, 12:20 p.m. | Last Modified: 1 Jun 2023, 12:20 p.m.
Panel Version: 0.25
GOF variants are associated with Protoporphyria, erythropoietic, XL, affecting hemizygous males and some het females (the phenotype in hete females ranges from asymptomatic to as severe as in affected males; reduced penetrance in females). LOF variants are associated with Anemia, sideroblastic, 1, XLR, affecting both hemizygous males and biallelic females. Both conditions included in newborns. Sources: Expert listCreated: 10 Mar 2023, 11:03 a.m. | Last Modified: 10 Mar 2023, 11:03 a.m.
Panel Version: 0.5
MOI reviewed by clinical team. Katrina Stone comment: From genereview: Although sometimes considered a synonym for XLP, the term erythropoietic protoporphyria, X-linked dominant is incorrect and should not be used: in all X-linked metabolic disorders the phenotype in heterozygous females can range from asymptomatic to as severe as that seen in affected male relatives. Mafalda Gomes comment: GOF variants are associated with Protoporphyria, erythropoietic, XL, affecting hemizygous males and some het females (the phenotype in hete females ranges from asymptomatic to as severe as in affected males; reduced penetrance in females).Created: 10 Mar 2023, 10:37 a.m. | Last Modified: 10 Mar 2023, 10:37 a.m.
Panel Version: 0.4
Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes
Protoporphyria, erythropoietic, X-linked
Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Details
- Mode of Inheritance
- X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
- Sources
-
- Expert Review Green
- Phenotypes
-
- Protoporphyria, erythropoietic, X-linked
- Tags
- OMIM
- 301300
- Clinvar variants
- Variants in ALAS2
- Penetrance
- None
- 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
-
- Cutaneous photosensitivity with a likely genetic cause
- Undiagnosed metabolic disorders
- Cytopenias and congenital anaemias
- Vascular skin disorders
- Non-acute porphyrias
- Adult onset neurodegenerative disorder
- Likely inborn error of metabolism
- Erythropoietic protoporphyria, mild variant
- Ataxia and cerebellar anomalies - narrow panel
- Childhood onset dystonia, chorea or related movement disorder
- Hereditary ataxia with onset in adulthood
- Mitochondrial disorders
- Iron metabolism disorders - NOT common HFE mutations
- Hereditary ataxia
- Rare anaemia
History Filter Activity
Added Tag
Arina Puzriakova (Genomics England Curator)Tag special_consideration tag was added to gene: ALAS2.
Set mode of inheritance
Ivone Leong (Genomics England Curator)Mode of inheritance for gene: ALAS2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Added Tag
Mafalda Gomes (Genomics England Curator)Tag internal_inclusion_list_only tag was added to gene: ALAS2.
Set Phenotypes
Mafalda Gomes (Genomics England Curator)Added phenotypes Protoporphyria, erythropoietic, X-linked for gene: ALAS2
Added New Source, Set Phenotypes, Status Update
Mafalda Gomes (Genomics England Curator)Source Expert Review Green was added to ALAS2. Added phenotypes Protoporphyria, erythropoietic, X-linked for gene: ALAS2 Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Removed Tag
Mafalda Gomes (Genomics England Curator)Tag GOF was removed from gene: ALAS2.
Added New Source, Set Phenotypes, Status Update
Mafalda Gomes (Genomics England Curator)Source Expert Review Amber was added to ALAS2. Added phenotypes Protoporphyria, erythropoietic, X-linked for gene: ALAS2 Rating Changed from No List (delete) to Amber List (moderate evidence)
Added New Source, Status Update
Mafalda Gomes (Genomics England Curator)Source Expert Review Removed was added to ALAS2. Rating Changed from Amber List (moderate evidence) to No List (delete)
Set mode of inheritance
Mafalda Gomes (Genomics England Curator)Mode of inheritance for gene: ALAS2 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Added Tag
Mafalda Gomes (Genomics England Curator)Tag GOF tag was added to gene: ALAS2.
Removed Tag
Mafalda Gomes (Genomics England Curator)Tag clinical_reviewed was removed from gene: ALAS2.
Added Tag
Mafalda Gomes (Genomics England Curator)Tag clinical_reviewed tag was added to gene: ALAS2.
Created, Added New Source, Set mode of inheritance, Set Phenotypes, Set mode of pathogenicity
Mafalda Gomes (Genomics England Curator)gene: ALAS2 was added gene: ALAS2 was added to Newborns additional phenotypes panel. Sources: Expert Review Amber Mode of inheritance for gene: ALAS2 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Phenotypes for gene: ALAS2 were set to Protoporphyria, erythropoietic, X-linked Mode of pathogenicity for gene: ALAS2 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments