ClinVar Genomic variation as it relates to human health
NM_000152.5(GAA):c.1552-13G>A
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000152.5(GAA):c.1552-13G>A
Variation ID: 255353 Accession: VCV000255353.51
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q25.3 17: 80110928 (GRCh38) [ NCBI UCSC ] 17: 78084727 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Oct 3, 2016 Oct 8, 2024 Apr 18, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000152.5:c.1552-13G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
intron variant NM_001079803.3:c.1552-13G>A intron variant NM_001079804.3:c.1552-13G>A intron variant NC_000017.11:g.80110928G>A NC_000017.10:g.78084727G>A NG_009822.1:g.14373G>A LRG_673:g.14373G>A LRG_673t1:c.1552-13G>A - Protein change
- Other names
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- Canonical SPDI
- NC_000017.11:80110927:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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0.00280 (A)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00272
The Genome Aggregation Database (gnomAD) 0.00276
The Genome Aggregation Database (gnomAD), exomes 0.00278
1000 Genomes Project 0.00280
1000 Genomes Project 30x 0.00281
Trans-Omics for Precision Medicine (TOPMed) 0.00283
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00308
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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GAA | - | - |
GRCh38 GRCh38 GRCh37 |
2797 | 2848 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Likely benign (4) |
criteria provided, multiple submitters, no conflicts
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Jan 25, 2018 | RCV000246280.12 | |
Likely benign (5) |
reviewed by expert panel
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Apr 18, 2023 | RCV000392826.26 | |
Likely benign (4) |
criteria provided, multiple submitters, no conflicts
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Aug 1, 2024 | RCV000786312.25 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Likely benign
(Apr 18, 2023)
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reviewed by expert panel
Method: curation
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Glycogen storage disease, type II
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
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ClinGen Lysosomal Storage Disorder Variant Curation Expert Panel
FDA Recognized Database
Accession: SCV004009591.1 First in ClinVar: Jul 08, 2023 Last updated: Jul 08, 2023 |
Comment:
The NM_000152.5:c.1552-13G>A variant is located near the acceptor splice region of intron 10 of GAA. The computational splicing predictor SpliceAI predicts that the variant has … (more)
The NM_000152.5:c.1552-13G>A variant is located near the acceptor splice region of intron 10 of GAA. The computational splicing predictor SpliceAI predicts that the variant has no impact on splicing (BP4). To our knowledge, functional studies investigating the impact of this variant on splicing are not available. The highest population minor allele frequency in gnomAD v2.1.1 is 0.004705 (607/129008 alleles) in the European non-Finnish population, which meets the ClinGen LSD VCEP’s threshold for BS1 (>0.005) when rounded up (BS1). There are 2 homozygotes in gnomAD v2.1.1. The variant was reported in a patient with Pompe disease along with a variant that has been classified as pathogenic by the ClinGen LD VCEP (c.841C>T (p.Arg281Trp); the phase was not reported in that patient (PMID: 31086307). However, analysis of clinical laboratory data in multiple patients with these two variants indicates that they likely occur in cis. There is a ClinVar entry for this variant (Variation ID: 255353). In summary, this variant meets the criteria to be classified as likely benign for Pompe disease. GAA-specific ACMG/AMP criteria met, as specified by the ClinGen Lysosomal Diseases Variant Curation Expert Panel (Specifications Version 2.0): BS1, BP4. Classification approved by the ClinGen Lysosomal Diseases Variant Curation Expert Panel, April 18th, 2023). (less)
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Likely benign
(-)
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criteria provided, single submitter
Method: clinical testing
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NOT SPECIFIED
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV000302663.1
First in ClinVar: Oct 03, 2016 Last updated: Oct 03, 2016 |
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Likely benign
(Dec 16, 2015)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000338203.4
First in ClinVar: Dec 06, 2016 Last updated: Apr 09, 2018 |
Number of individuals with the variant: 1
Sex: mixed
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Likely benign
(Jan 25, 2018)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000917387.1
First in ClinVar: Jun 02, 2019 Last updated: Jun 02, 2019 |
Comment:
Variant summary: The GAA c.1552-13G>A variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a benign outcome for this variant. … (more)
Variant summary: The GAA c.1552-13G>A variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 788/277130 control chromosomes (2 homozygotes), predominantly observed in the European (Non-Finnish) subpopulation at a frequency of 0.004675 (592/126628)(gnomAD). This frequency is slightly above the estimated maximal expected allele frequency of a pathogenic GAA variant (0.0042205), suggesting this is likely a benign polymorphism found primarily in the populations of European (Non-Finnish) origin. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign and one other lab classified it as VUS. Taken together, this variant is classified as likely benign. (less)
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Uncertain significance
(Jan 13, 2018)
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criteria provided, single submitter
Method: clinical testing
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Glycogen storage disease, type II
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000407282.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. (less)
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Likely benign
(Jul 08, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000724576.4
First in ClinVar: Apr 09, 2018 Last updated: Mar 04, 2023 |
Comment:
See Variant Classification Assertion Criteria.
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Likely benign
(Jan 22, 2020)
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criteria provided, single submitter
Method: curation
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Glycogen storage disease, type II
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
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Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard
Accession: SCV001423080.2
First in ClinVar: Jul 19, 2020 Last updated: Jan 29, 2022 |
Comment:
The c.1552-13G>A variant in GAA has not been previously reported in individuals with Glycogen Storage Disease II but has been reported as a likely benign … (more)
The c.1552-13G>A variant in GAA has not been previously reported in individuals with Glycogen Storage Disease II but has been reported as a likely benign variant (by GeneDx, EGL, and Prevention Genetics) and as a VUS (by Illumina) in ClinVar (Variation ID: 255353). This variant has been identified in 0.4705% (607/129008) of European (non-Finnish) chromosomes, including 2 homozygotes, by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs111261964). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. Computational prediction tools and conservation analyses suggest that this variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. However, novel synonymous variants supported by computational evidence without raised suspicion for an impact are likely benign (PMID: 25741868). In summary, although additional studies are required to fully establish its clinical significance, this variant is likely benign. ACMG/AMP Criteria applied: BP4, BP7 (Richards 2015). (less)
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Likely benign
(Oct 21, 2022)
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criteria provided, single submitter
Method: clinical testing
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Glycogen storage disease, type II
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV001471012.4
First in ClinVar: Jan 26, 2021 Last updated: Mar 04, 2023 |
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Benign
(Feb 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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Glycogen storage disease, type II
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001731733.5
First in ClinVar: Jun 15, 2021 Last updated: Feb 20, 2024 |
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Likely benign
(Aug 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV002063662.19
First in ClinVar: Jan 29, 2022 Last updated: Oct 08, 2024 |
Comment:
GAA: BS2
Number of individuals with the variant: 20
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Uncertain significance
(Feb 17, 2011)
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no assertion criteria provided
Method: provider interpretation
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not provided
Affected status: unknown
Allele origin:
germline
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Stanford Center for Inherited Cardiovascular Disease, Stanford University
Accession: SCV000925081.1
First in ClinVar: Jun 30, 2019 Last updated: Jun 30, 2019 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001931932.1 First in ClinVar: Sep 25, 2021 Last updated: Sep 25, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001971118.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
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Germline Functional Evidence
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 germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Targeted exome sequencing for mitochondrial disorders reveals high genetic heterogeneity. | DaRe JT | BMC medical genetics | 2013 | PMID: 24215330 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=GAA | - | - | - | - |
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/9e7461e9-74b8-465f-91f5-afa2ba0779a6 | - | - | - | - |
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/fe68b874-6770-4b68-9d65-68ee9e8d018f | - | - | - | - |
Text-mined citations for rs111261964 ...
HelpRecord last updated Oct 08, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.