ClinVar Genomic variation as it relates to human health
NM_000152.5(GAA):c.2780C>T (p.Thr927Ile)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000152.5(GAA):c.2780C>T (p.Thr927Ile)
Variation ID: 92482 Accession: VCV000092482.29
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q25.3 17: 80118786 (GRCh38) [ NCBI UCSC ] 17: 78092585 (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 Jul 6, 2014 Sep 29, 2024 Jan 23, 2020 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000152.5:c.2780C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000143.2:p.Thr927Ile missense NM_001079803.3:c.2780C>T NP_001073271.1:p.Thr927Ile missense NM_001079804.3:c.2780C>T NP_001073272.1:p.Thr927Ile missense NC_000017.11:g.80118786C>T NC_000017.10:g.78092585C>T NG_009822.1:g.22231C>T LRG_673:g.22231C>T LRG_673t1:c.2780C>T LRG_673p1:p.Thr927Ile P10253:p.Thr927Ile - Protein change
- T927I
- Other names
- -
- Canonical SPDI
- NC_000017.11:80118785:C:T
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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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0.05431 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.01880
Exome Aggregation Consortium (ExAC) 0.02202
The Genome Aggregation Database (gnomAD) 0.04402
Trans-Omics for Precision Medicine (TOPMed) 0.04469
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.04706
1000 Genomes Project 0.05431
1000 Genomes Project 30x 0.05778
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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Benign (5) |
criteria provided, multiple submitters, no conflicts
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Dec 10, 2015 | RCV000078178.29 | |
Benign (5) |
reviewed by expert panel
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Jan 23, 2020 | RCV000308857.25 | |
Benign (3) |
criteria provided, single submitter
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- | RCV000675250.15 | |
Benign (1) |
criteria provided, single submitter
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Mar 19, 2020 | RCV002433584.9 |
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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Benign
(Jan 23, 2020)
|
reviewed by expert panel
Method: curation
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Glycogen storage disease, type II
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
|
ClinGen Lysosomal Storage Disorder Variant Curation Expert Panel
FDA Recognized Database
Accession: SCV001371703.1 First in ClinVar: Jul 16, 2020 Last updated: Jul 16, 2020 |
Comment:
The highest continental population minor allele frequency for c.2780C>T (p.Thr927Ile) in gnomAD v2.1.1 is 0.1317 in the African population. This is higher than the ClinGen … (more)
The highest continental population minor allele frequency for c.2780C>T (p.Thr927Ile) in gnomAD v2.1.1 is 0.1317 in the African population. This is higher than the ClinGen LSD VCEP's BA1 threshold (>0.01), therefore meeting the BA1 criterion. There is a ClinVar entry for this variant (Variation ID: 92482; 2 star review status) with six submitters classifying the variant as benign, and two as likely benign. In summary, this variant meets the criteria to be classified as benign for Pompe disease. GAA-specific ACMG/AMP criteria applied, as specified by the ClinGen LSD VCEP: BA1. (less)
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Benign
(Mar 19, 2020)
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criteria provided, single submitter
Method: clinical testing
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Cardiovascular phenotype
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV002751682.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation … (more)
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
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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: SCV000302685.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
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Benign
(Dec 10, 2015)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000517803.4
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
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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: SCV000626601.6
First in ClinVar: Dec 26, 2017 Last updated: Feb 20, 2024 |
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Benign
(-)
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criteria provided, single submitter
Method: not provided
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not provided
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Breakthrough Genomics, Breakthrough Genomics
Accession: SCV005248767.1
First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024 |
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Benign
(Aug 01, 2017)
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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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Phosphorus, Inc.
Accession: SCV000679768.1
First in ClinVar: Dec 26, 2017 Last updated: Dec 26, 2017 |
Number of individuals with the variant: 1
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Benign
(Aug 13, 2013)
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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: SCV000110016.8
First in ClinVar: Jan 17, 2014 Last updated: May 03, 2018 |
Number of individuals with the variant: 8
Sex: mixed
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Benign
(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: SCV000407306.3
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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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AllHighlyPenetrant
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV000151259.2
First in ClinVar: May 17, 2014 Last updated: Jul 06, 2014 |
Comment:
Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated … (more)
Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. (less)
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Benign
(Sep 16, 2020)
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no assertion criteria provided
Method: clinical testing
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Glycogen storage disease type II
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV001463867.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
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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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Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Study: VKGL Data-share Consensus
Accession: SCV001799730.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 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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Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001929227.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
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Benign
(May 17, 2017)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV000800897.1
First in ClinVar: Aug 05, 2018 Last updated: Aug 05, 2018 |
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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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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 |
Free the data: one laboratory's approach to knowledge-based genomic variant classification and preparation for EMR integration of genomic data. | Bean LJ | Human mutation | 2013 | PMID: 23757202 |
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 |
Broad spectrum of Pompe disease in patients with the same c.-32-13T->G haplotype. | Kroos MA | Neurology | 2007 | PMID: 17210890 |
Mutation detection in glycogen storage-disease type II by RT-PCR and automated sequencing. | Hermans MM | Biochemical and biophysical research communications | 1997 | PMID: 9425285 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=GAA | - | - | - | - |
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/0dace307-d73d-4361-89ee-42f551fed0d7 | - | - | - | - |
Text-mined citations for rs1800315 ...
HelpRecord last updated Sep 29, 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.