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NM_000152.5(GAA):c.118C>T (p.Arg40Ter)

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Interpretation:
Pathogenic​

Review status:
reviewed by expert panel FDA Recognized Database
Submissions:
5 (Most recent: Jan 7, 2021)
Last evaluated:
Apr 6, 2020
Accession:
VCV000426593.5
Variation ID:
426593
Description:
single nucleotide variant
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NM_000152.5(GAA):c.118C>T (p.Arg40Ter)

Allele ID
415589
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
17q25.3
Genomic location
17: 80104704 (GRCh38) GRCh38 UCSC
17: 78078503 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000017.10:g.78078503C>T
NC_000017.11:g.80104704C>T
NM_000152.5:c.118C>T MANE Select NP_000143.2:p.Arg40Ter nonsense
... more HGVS
Protein change
R40*
Other names
-
Canonical SPDI
NC_000017.11:80104703:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD) 0.00003
Exome Aggregation Consortium (ExAC) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00001
Links
ClinGen: CA8814791
dbSNP: rs767409395
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 4 reviewed by expert panel Apr 6, 2020 RCV000589039.4
Pathogenic 1 criteria provided, single submitter Nov 22, 2018 RCV000489843.2
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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
Pathogenic
(Apr 06, 2020)
reviewed by expert panel
Method: curation
Glycogen storage disease, type II
(Autosomal recessive inheritance)
Allele origin: germline
ClinGen Lysosomal Storage Disorder Variant Curation Expert Panel, ClinGen
FDA Recognized Database
Accession: SCV001371737.1
Submitted: (May 29, 2020)
Evidence details
Publications
PubMed (5)
Other databases
https://erepo.clinicalgenome.org…
Comment:
This nonsense variant, c.118C>T (p.Arg40Ter), is expected to result in a premature termination codon, nonsense mediated decay, and absence of gene product, meeting PVS1. The … (more)
Pathogenic
(Feb 03, 2016)
criteria provided, single submitter
Method: clinical testing
Glycogen storage disease, type II
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000695642.1
Submitted: (Jan 25, 2018)
Evidence details
Publications
PubMed (4)
Comment:
Variant summary: The c.118C>T variant in GAA is a nonsense mutation. The mutation is predicted to lead to a truncated/absent protein. It has been reported … (more)
Pathogenic
(Nov 22, 2018)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000577073.4
Submitted: (Jan 29, 2019)
Evidence details
Comment:
The R40X pathogenic variant in the GAA gene has been reported previously in multiple individuals with glycogen storage disease type II in the homozygous state, … (more)
Pathogenic
(Aug 29, 2020)
criteria provided, single submitter
Method: clinical testing
Glycogen storage disease, type II
Allele origin: germline
Invitae
Accession: SCV001587223.1
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (4)
Comment:
This sequence change creates a premature translational stop signal (p.Arg40*) in the GAA gene. It is expected to result in an absent or disrupted protein … (more)
Pathogenic
(Nov 18, 2019)
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: SCV001422669.1
Submitted: (Mar 09, 2020)
Evidence details
Publications
PubMed (8)
Other databases
https://erepo.clinicalgenome.org…
Comment:
The p.Arg40Ter variant in GAA has been reported in at least 12 individuals (7 Italian, 1 German, 1 French, 1 Portuguese, and 1 Pakistani individuals) … (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
A New Integrated Newborn Screening Workflow Can Provide a Shortcut to Differential Diagnosis and Confirmation of Inherited Metabolic Diseases. Ko JM Yonsei medical journal 2018 PMID: 29869463
A molecular analysis of the GAA gene and clinical spectrum in 38 patients with Pompe disease in Japan. Fukuhara Y Molecular genetics and metabolism reports 2017 PMID: 29124014
Clinical and molecular genetic study of infantile-onset Pompe disease in Chinese patients: identification of 6 novel mutations. Fu L Gene 2014 PMID: 24269976
Distinct disease phenotypes linked to different combinations of GAA mutations in a large late-onset GSDII sibship. Sampaolo S Orphanet journal of rare diseases 2013 PMID: 24107549
Auditory system involvement in late onset Pompe disease: a study of 20 Italian patients. Musumeci O Molecular genetics and metabolism 2012 PMID: 22958975
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
Predicting cross-reactive immunological material (CRIM) status in Pompe disease using GAA mutations: lessons learned from 10 years of clinical laboratory testing experience. Bali DS American journal of medical genetics. Part C, Seminars in medical genetics 2012 PMID: 22252923
Abnormalities of cerebral arteries are frequent in patients with late-onset Pompe disease. Sacconi S Journal of neurology 2010 PMID: 20559845
Update of the Pompe disease mutation database with 107 sequence variants and a format for severity rating. Kroos M Human mutation 2008 PMID: 18425781
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
Juvenile and adult-onset acid maltase deficiency in France: genotype-phenotype correlation. Laforêt P Neurology 2000 PMID: 11071489
A novel acid alpha-glucosidase mutation identified in a Pakistani family with glycogen storage disease type II. Kroos MA Journal of inherited metabolic disease 1997 PMID: 9266392
Glycogenosis type II (acid maltase deficiency). Reuser AJ Muscle & nerve. Supplement 1995 PMID: 7603530
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/79019119-b26c-4336-8958-b3272cd7e778 - - - -
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/b83bdb13-e262-4abd-a20a-ab659995e215 - - - -

Text-mined citations for rs767409395...

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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