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NM_000049.3(ASPA):c.854A>C (p.Glu285Ala)

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Interpretation:
Pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
9 (Most recent: Mar 28, 2019)
Last evaluated:
Jan 6, 2019
Accession:
VCV000002605.3
Variation ID:
2605
Description:
single nucleotide variant
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NM_000049.3(ASPA):c.854A>C (p.Glu285Ala)

Allele ID
17644
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
17p13.2
Genomic location
17: 3499000 (GRCh38) GRCh38 UCSC
17: 3402294 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000017.10:g.3402294A>C
NC_000017.11:g.3499000A>C
NM_000049.3:c.854A>C NP_000040.1:p.Glu285Ala missense
... more HGVS
Protein change
E285A
Other names
854A-C
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD), exomes 0.00043
The Genome Aggregation Database (gnomAD) 0.00016
Exome Aggregation Consortium (ExAC) 0.00036
Trans-Omics for Precision Medicine (TOPMed) 0.00022
Links
ClinGen: CA325511
UniProtKB: P45381#VAR_004999
OMIM: 608034.0001
dbSNP: rs28940279
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 6 criteria provided, multiple submitters, no conflicts Jan 6, 2019 RCV000002723.14
Pathogenic 2 criteria provided, multiple submitters, no conflicts Oct 23, 2017 RCV000420704.3
Pathogenic 1 criteria provided, single submitter Jun 25, 2016 RCV000590467.1
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
ASPA - - GRCh38
GRCh37
3 133
SPATA22 - - GRCh38
GRCh37
- 203

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Oct 23, 2017)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000512105.3
Submitted: (Nov 28, 2017)
Evidence details
Comment:
The E285A variant accounts for approximately 85% of disease-causing ASPA alleles in Ashkenazi Jewish patients with Canavan disease (Kaul et al. 1993). Expression studies found ... (more)
Pathogenic
(Jun 13, 2015)
criteria provided, single submitter
Method: clinical testing
Spongy degeneration of central nervous system
Allele origin: unknown
Counsyl
Accession: SCV000677947.1
Submitted: (Jun 22, 2017)
Evidence details
Publications
PubMed (3)
Pathogenic
(Jun 25, 2016)
criteria provided, single submitter
Method: clinical testing
Canavan Disease, Familial Form
Allele origin: germline
Integrated Genetics/Laboratory Corporation of America
Accession: SCV000694157.1
Submitted: (Jan 25, 2018)
Evidence details
Publications
PubMed (3)
Comment:
Variant summary: The ASPA c.854A>C (p.Glu285Ala) variant involves the alteration of a conserved nucleotide. Glu285 is predicted to be part of the catalytic domain of ... (more)
Pathogenic
(Jan 15, 2016)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics
Accession: SCV000231463.5
Submitted: (Sep 19, 2018)
Evidence details
Other databases
http://www.egl-eurofins.com/em...
Pathogenic
(Jan 06, 2019)
criteria provided, single submitter
Method: clinical testing
Spongy degeneration of central nervous system
Allele origin: germline
Invitae
Accession: SCV000218961.6
Submitted: (Mar 28, 2019)
Evidence details
Publications
PubMed (3)
Comment:
This sequence change replaces glutamic acid with alanine at codon 285 of the aspartoacylase protein (p.Glu285Ala). The glutamic acid residue is highly conserved and there ... (more)
Pathogenic
(Oct 02, 2014)
criteria provided, single submitter
Method: clinical testing
Spongy degeneration of central nervous system
(Autosomal recessive inheritance)
Allele origin: germline
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine
Accession: SCV000245578.2
Submitted: (Mar 21, 2019)
Evidence details
Publications
PubMed (2)
Comment:
The p.Glu285Ala variant in ASPA is one of the most frequent pathogenic variants implicated in Canavan disease and has been reported in at least 19 ... (more)
Pathogenic
(Oct 31, 2018)
criteria provided, single submitter
Method: clinical testing
Spongy degeneration of central nervous system
Allele origin: unknown
Fulgent Genetics,Fulgent Genetics
Accession: SCV000894113.1
Submitted: (Nov 14, 2018)
Evidence details
Publications
PubMed (1)
DOI: 10.1038/gim.2015.30
Pathogenic
(Nov 24, 2018)
criteria provided, single submitter
Method: clinical testing
Spongy degeneration of central nervous system
Allele origin: germline
Illumina Clinical Services Laboratory,Illumina
Accession: SCV000914761.1
Submitted: (Feb 01, 2019)
Evidence details
Publications
PubMed (3)
Comment:
The ASPA c.854A>C (p.Glu285Ala) missense variant has been reported in two studies in which it was found in a total of 19 individuals with Canavan ... (more)
Pathogenic
(Aug 01, 1994)
no assertion criteria provided
Method: literature only
CANAVAN DISEASE
Allele origin: germline
OMIM
Accession: SCV000022881.1
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (2)

Citations for this variant

Title Author Journal Year Link
Canavan Disease Matalon R - 2018 PMID: 20301412
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Richards S Genetics in medicine : official journal of the American College of Medical Genetics 2015 PMID: 25741868
Aspartoacylase catalytic deficiency as the cause of Canavan disease: a structural perspective. Wijayasinghe YS Biochemistry 2014 PMID: 25003821
Relationship between enzyme properties and disease progression in Canavan disease. Zano S Journal of inherited metabolic disease 2013 PMID: 22850825
Identification and expression of eight novel mutations among non-Jewish patients with Canavan disease. Kaul R American journal of human genetics 1996 PMID: 8659549
The frequency of the C854 mutation in the aspartoacylase gene in Ashkenazi Jews in Israel. Elpeleg ON American journal of human genetics 1994 PMID: 8037206
Cloning of the human aspartoacylase cDNA and a common missense mutation in Canavan disease. Kaul R Nature genetics 1993 PMID: 8252036
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=ASPA - - - -

Record last updated Oct 27, 2019