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NM_000152.5(GAA):c.2214G>A (p.Trp738Ter)

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Interpretation:
Pathogenic​

Review status:
reviewed by expert panel FDA Recognized Database
Submissions:
5 (Most recent: Nov 16, 2021)
Last evaluated:
Oct 5, 2020
Accession:
VCV000370223.6
Variation ID:
370223
Description:
single nucleotide variant
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NM_000152.5(GAA):c.2214G>A (p.Trp738Ter)

Allele ID
358513
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
17q25.3
Genomic location
17: 80116992 (GRCh38) GRCh38 UCSC
17: 78090791 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
LRG_673:g.20437G>A
LRG_673t1:c.2214G>A
NM_000152.5(GAA):c.2214G>A MANE Select
... more HGVS
Protein change
W738*
Other names
-
Canonical SPDI
NC_000017.11:80116991:G:A
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD), exomes 0.00000
Links
ClinGen: CA16041901
dbSNP: rs1057516328
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 5 reviewed by expert panel Oct 5, 2020 RCV000409827.6
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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
(Oct 05, 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: SCV001443322.1
Submitted: (Nov 13, 2020)
Evidence details
Publications
PubMed (5)
Other databases
https://erepo.clinicalgenome.org…
Comment:
This variant, c.2214G>A (p.Trp738Ter), is a nonsense variant that is predicted to result in nonsense-mediated decay and lack of gene product, meeting PVS1. The highest … (more)
Likely pathogenic
(Dec 15, 2015)
criteria provided, single submitter
Method: clinical testing
Glycogen storage disease, type II
Allele origin: unknown
Counsyl
Accession: SCV000485477.1
Submitted: (Nov 23, 2016)
Evidence details
Publications
PubMed (1)
Pathogenic
(Oct 07, 2020)
criteria provided, single submitter
Method: clinical testing
Glycogen storage disease, type II
Allele origin: germline
Invitae
Accession: SCV001211539.2
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (3)
Comment:
This sequence change creates a premature translational stop signal (p.Trp738*) in the GAA gene. It is expected to result in an absent or disrupted protein … (more)
Pathogenic
(Oct 25, 2021)
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: SCV002015051.1
Submitted: (Nov 16, 2021)
Evidence details
Publications
PubMed (3)
Comment:
Variant summary: GAA c.2214G>A (p.Trp738X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
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: SCV001422610.1
Submitted: (Mar 09, 2020)
Evidence details
Publications
PubMed (2)
Other databases
https://erepo.clinicalgenome.org…
Comment:
The p.Trp738Ter variant in GAA has been reported in 2 Chinese and 2 German individuals with Glycogen Storage Disease II, segregated with disease in 2 … (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
2-deoxy-2-[18]fluoro-D-glucose PET/CT (18FDG PET/CT) may not be a viable biomarker in Pompe disease. Plöckinger U Human genomics 2018 PMID: 29523196
[Clinical characteristics and gene mutation analysis of one pedigree with infantile glycogen storage disease type II]. Zhang L Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics 2015 PMID: 26575883
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
[Application of enzyme assay and gene analysis in the prenatal diagnosis for a family with glycogen storage disease type II]. Zeng MH Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 2011 PMID: 21644219
Diagnostic efficacy of the fluorometric determination of enzyme activity for Pompe disease from dried blood specimens compared with lymphocytes-possibility for newborn screening. Lukacs Z Journal of inherited metabolic disease 2010 PMID: 20033296
Update of the Pompe disease mutation database with 107 sequence variants and a format for severity rating. Kroos M Human mutation 2008 PMID: 18425781
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/21ce77bb-478f-40a2-852d-0621f1432c0b - - - -
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/ed960e3f-0822-43b8-8558-3a361d2331d7 - - - -

Text-mined citations for rs1057516328...

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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 Nov 20, 2021