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NM_000152.5(GAA):c.1561G>A (p.Glu521Lys)

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Interpretation:
Likely pathogenic​

Review status:
criteria provided, single submitter
Submissions:
3 (Most recent: Mar 9, 2020)
Last evaluated:
Nov 20, 2014
Accession:
VCV000004022.2
Variation ID:
4022
Description:
single nucleotide variant
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NM_000152.5(GAA):c.1561G>A (p.Glu521Lys)

Allele ID
19061
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
17q25.3
Genomic location
17: 80110950 (GRCh38) GRCh38 UCSC
17: 78084749 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000017.10:g.78084749G>A
NC_000017.11:g.80110950G>A
NM_000152.5:c.1561G>A MANE Select NP_000143.2:p.Glu521Lys missense
... more HGVS
Protein change
E521K
Other names
-
Canonical SPDI
NC_000017.11:80110949:G:A
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
Exome Aggregation Consortium (ExAC) 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00000
Links
ClinGen: CA116593
UniProtKB: P10253#VAR_004295
OMIM: 606800.0003
dbSNP: rs121907937
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely pathogenic 2 criteria provided, single submitter Nov 20, 2014 RCV000169465.2
Pathogenic 1 no assertion criteria provided Sep 16, 1991 RCV000004237.3
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
GAA - - GRCh38
GRCh37
1519 1559

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(Nov 20, 2014)
criteria provided, single submitter
Method: literature only
Glycogen storage disease, type II
(Autosomal recessive inheritance)
Allele origin: unknown
Counsyl
Accession: SCV000220900.1
Submitted: (Mar 11, 2015)
Evidence details
Publications
PubMed (10)
Pathogenic
(Sep 16, 1991)
no assertion criteria provided
Method: literature only
GLYCOGEN STORAGE DISEASE II, INFANTILE FORM
Allele origin: germline
OMIM
Accession: SCV000024403.2
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (1)
Pathogenic
(Jan 22, 2020)
no assertion criteria provided
Method: curation
Glycogen storage disease, type II
(Autosomal recessive inheritance)
Allele origin: germline
Broad Institute Rare Disease Group, Broad Institute
Accession: SCV001423119.1
Submitted: (Mar 09, 2020)
Evidence details
Other databases
https://erepo.clinicalgenome.org…
Comment:
The p.Glu521Lys variant in GAA has been reported in 11 individuals (including at least 3 Caucasian and 2 Indian individuals) with Glycogen Storage Disease II, … (more)

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Proteome-wide analysis of nonsynonymous single-nucleotide variations in active sites of human proteins. Dingerdissen H The FEBS journal 2013 PMID: 23350563
Trunk muscle involvement in late-onset Pompe disease: study of thirty patients. Alejaldre A Neuromuscular disorders : NMD 2012 PMID: 22980766
Can genes influencing muscle function affect the therapeutic response to enzyme replacement therapy (ERT) in late-onset type II glycogenosis? Ravaglia S Molecular genetics and metabolism 2012 PMID: 22704482
A cross-sectional single-centre study on the spectrum of Pompe disease, German patients: molecular analysis of the GAA gene, manifestation and genotype-phenotype correlations. Herzog A Orphanet journal of rare diseases 2012 PMID: 22676651
Expanding the clinical spectrum of late-onset Pompe disease: dilated arteriopathy involving the thoracic aorta, a novel vascular phenotype uncovered. El-Gharbawy AH Molecular genetics and metabolism 2011 PMID: 21605996
The pharmacological chaperone 1-deoxynojirimycin increases the activity and lysosomal trafficking of multiple mutant forms of acid alpha-glucosidase. Flanagan JJ Human mutation 2009 PMID: 19862843
Development of a clinical assay for detection of GAA mutations and characterization of the GAA mutation spectrum in a Canadian cohort of individuals with glycogen storage disease, type II. McCready ME Molecular genetics and metabolism 2007 PMID: 17723315
Glycogen storage disease: clinical, biochemical, and molecular heterogeneity. Shin YS Seminars in pediatric neurology 2006 PMID: 17027861
Mechanistic and structural analysis of a family 31 alpha-glycosidase and its glycosyl-enzyme intermediate. Lovering AL The Journal of biological chemistry 2005 PMID: 15501829
Identification of a point mutation in the human lysosomal alpha-glucosidase gene causing infantile glycogenosis type II. Hermans MM Biochemical and biophysical research communications 1991 PMID: 1898413
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/eedd1814-a931-4f09-a60f-5fafa4199742 - - - -

Text-mined citations for rs121907937...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Aug 27, 2021