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rs28940279

From SNPedia

Canavan disease
Orientationplus
Stabilizedplus
Geno Mag Summary
(A;A) 0 common in clinvar
(A;C) 2.5 carrier for Canavan disease
(C;C) 4 Canavan disease
ReferenceGRCh38 38.1/141
Chromosome17
Position3499000
GeneASPA, SPATA22
is asnp
is mentioned by
dbSNPrs28940279
ebirs28940279
HLIrs28940279
Exacrs28940279
Varsomers28940279
Maprs28940279
PheGenIrs28940279
hapmaprs28940279
1000 genomesrs28940279
hgdprs28940279
ensemblrs28940279
gopubmedrs28940279
geneviewrs28940279
scholarrs28940279
googlers28940279
pharmgkbrs28940279
gwascentralrs28940279
openSNPrs28940279
23andMers28940279
23andMe allrs28940279
SNP Nexus

SNPshotrs28940279
SNPdbers28940279
MSV3drs28940279
GWAS Ctlgrs28940279
Max Magnitude4
OMIM608034
DescCanavan disease
Variant0001
Relatedalso
Neighborrs28940574
Distance60


ClinVar
Risk rs28940279(C;C)
Alt rs28940279(C;C)
Reference rs28940279(A;A)
Significance Pathogenic
Disease Spongy degeneration of central nervous system
Variation info
Gene ASPA SPATA22
CLNDBN Spongy degeneration of central nervous system
Reversed 0
HGVS NC_000017.10:g.3402294A>C
CLNSRC OMIM Allelic Variant
CLNACC RCV000002723.5,



rs28940279, also known as E285A or Glu285Ala, is a SNP in the ASPA gene.

rs28940279 is one of several known causal SNPs of Canavan disease. Canavan disease is a degenerative disease of the nervous system. It is a childhood onset disease which begins in early infancy. It is characterized by disordered muscular behavior (e.g., hypotonia, hyperextension) and neurological symptoms, such as blindness, developmental and cognitive delays. The neurological findings appear to be due to demyelination and leukodystrophy. Histology indicates the presence of spongy degeneration; cytology confirms astrocytic swelling of normal neurons and abnormality of astrocyte mitochondria. [PMID 3354621] Ultimately, sufferers become extremely ill and die on average at 18 months of age.

rs28940279 is a SNP in the aspartoacylase ASPA gene. [PMID 8252036] The A-C transversion results in a substitution of alanine, a hydrophobic small-chain amino acid, for a glutamate (which is both large and charged). This substitution, E285A, is at a residue predicted to be part of the catalytic domain of aspartocyclase. This missense mutation is predicted to have drastic effects on the catalytic domain because of the vast difference between the amino acids.

In particular, this substitution is common in Ashkenazi Jews, with carrier frequency approximately 1 in 60 individuals. [PMID 8037206OA-icon.png] This suggests that some degree of founder effect is responsible for its prevalence within the Ashkenazi Jewish population. In particular, one study suspects that the mutation originated in the Vilna area, in Poland or Lithuania depending on the political timeperiod of origin. [PMID 14239091] This suggests that it is a newer variant than others found in the more broad European population.