Hereditary systemic amyloidosis

Gene: APOA2

Green List (high evidence)

APOA2 (apolipoprotein A2)
EnsemblGeneIds (GRCh38): ENSG00000158874
EnsemblGeneIds (GRCh37): ENSG00000158874
OMIM: 107670, Gene2Phenotype
APOA2 is in 4 panels

1 review

Eleanor Williams (Genomics England Curator)

Green List (high evidence)

Not associated with a relevant phenotype in OMIM but publications support association

4 cases reported:

PMID: 29270531 - Prokaeva et al 2017 - report a family with renal amyloidosis associated with a novel stop codon mutation in APOA2 and the apoA-II variant, 78Leuext21
PMID: 12787390 - Yazaki et al 2003 - a Caucasian man with progressive renal dysfunction found to have amyloidosis. DNA sequencing of the apoAII gene in the proband showed a T to C transition at the first position of the stop codon indicating replacement of the stop codon by l-arginine (Arg) at residue 78. DNA from other family members was not available.
PMID: 11401442 - Benson et al 2001 - report a family with hereditary renal amyloidosis. Sequence analysis of the apoAII gene of affected individuals showed heterozygosity for a single base substitution in the apoAII stop codon. The mutation results in extension of translation to the next in-frame stop codon 60 nucleotides downstream and is predicted to give a 21-residue C-terminal extension of the apoAII protein identical to that found in the amyloid.
PMID: 11703582 - Yazaki et al 2001 - Caucasian male with proteinuria and renal biopsy revealed amyloid deposition in glomeruli. DNA analysis revealed heterozygosity for a G to C transversion at the second position of the stop-codon of apoA-II gene, suggesting a stop to serine substitution at codon 78. Western blot analysis and amino acid sequence analysis of the patient's plasma apoA-II showed both normal apoA-II and variant apoA-II with a 21-amino acid residue extension at the C-terminus.
Created: 13 Aug 2019, 10:57 a.m. | Last Modified: 13 Aug 2019, 10:57 a.m.
Panel Version: 0.7
This gene was part of an initial gene list collated by Emma Ashton (NE Thames Regional Genetics laboratory, GOSH NHS Foundation Trust) January 2019 on behalf of the GMS Renal Specialist Test Group.Gene Symbol submitted: APOA2;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. Other Comments: Already on the Periodic Fever Syndrome App
Created: 2 Feb 2019, 3:49 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted


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


Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
  • Expert Review Green
Clinvar variants
Variants in APOA2
Panels with this gene

History Filter Activity

2 Feb 2019, Gel status: 4

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

Eleanor Williams (Genomics England Curator)

gene: APOA2 was added gene: APOA2 was added to Amyloidosis. Sources: Expert Review Green,NHS GMS Mode of inheritance for gene: APOA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: APOA2 were set to 29270531; 11703582; 12787390; 11401442