ClinVar Genomic variation as it relates to human health
NM_000158.4(GBE1):c.691+2T>C
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000158.4(GBE1):c.691+2T>C
Variation ID: 208584 Accession: VCV000208584.72
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 3p12.2 3: 81648854 (GRCh38) [ NCBI UCSC ] 3: 81698005 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Sep 14, 2015 Apr 15, 2024 Jan 30, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000158.4:c.691+2T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
splice donor NC_000003.12:g.81648854A>G NC_000003.11:g.81698005A>G NG_011810.1:g.117947T>C NG_011810.2:g.117791T>C - Protein change
- Other names
- -
- Canonical SPDI
- NC_000003.12:81648853:A:G
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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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0.00020 (G)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 0.00020
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00111
Trans-Omics for Precision Medicine (TOPMed) 0.00065
Exome Aggregation Consortium (ExAC) 0.00115
1000 Genomes Project 30x 0.00016
The Genome Aggregation Database (gnomAD) 0.00078
The Genome Aggregation Database (gnomAD), exomes 0.00089
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
Help
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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GBE1 | - | - |
GRCh38 GRCh37 |
974 | 990 |
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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Pathogenic (9) |
criteria provided, multiple submitters, no conflicts
|
Sep 13, 2023 | RCV000190589.25 | |
Pathogenic (14) |
criteria provided, multiple submitters, no conflicts
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Jan 1, 2024 | RCV000224184.51 | |
Pathogenic (1) |
criteria provided, single submitter
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Oct 13, 2017 | RCV000368399.13 | |
Pathogenic (1) |
criteria provided, single submitter
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May 10, 2022 | RCV000660553.16 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 30, 2024 | RCV000706641.14 | |
Pathogenic (1) |
criteria provided, single submitter
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Jun 16, 2020 | RCV001449661.12 | |
Pathogenic (1) |
criteria provided, single submitter
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Sep 28, 2023 | RCV003388833.2 | |
Pathogenic (1) |
criteria provided, single submitter
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Nov 1, 2023 | RCV003917726.1 |
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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Pathogenic
(Mar 05, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: not provided
Allele origin:
germline
|
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics
Accession: SCV000280944.1
First in ClinVar: Jun 08, 2016 Last updated: Jun 08, 2016 |
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Pathogenic
(Aug 03, 2017)
|
criteria provided, single submitter
Method: clinical testing
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Glycogen storage disease, type IV
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000792913.1
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
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Pathogenic
(Jun 02, 2016)
|
criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000342180.4
First in ClinVar: Dec 06, 2016 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 2
Sex: mixed
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Pathogenic
(Oct 13, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
GBE1-Related Disorders
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000446308.3
First in ClinVar: Dec 06, 2016 Last updated: May 24, 2019 |
Comment:
The GBE1 c.691+2T>C splice donor variant has been reported in a total of seven individuals, including five with glycogen storage disease type IV (GSD IV) … (more)
The GBE1 c.691+2T>C splice donor variant has been reported in a total of seven individuals, including five with glycogen storage disease type IV (GSD IV) and two with adult polyglucosan body disease (APBD) (Fernandez et al. 2010; Ravenscroft et al. 2013; Bendroth-Asmussen et al. 2016; Kuhn et al. 2016; Franco-Palacios et al. 2016; Lopez Chiriboga 2017). All five individuals with GSD IV and one individual with APBD were compound heterozygous for the variant. In addition, one individual with APBD was heterozygous for the c.691+2T>C variant and homozygous for another intronic variant in the GBE1 gene (Franco-Palacios et al. 2016). The c.691+2T>C variant was also identified in a heterozygous state in two unaffected individuals (Ravenscroft et al. 2013; Dainese et al. 2014). Control data are unavailable for this variant, which is reported at a frequency of 0.00196 in the European (non-Finnish) population of the Exome Aggregation Consortium. Two studies noted significantly reduced GBE enzyme activity in individual fibroblasts (Fernandez et al. 2010; Ravenscroft et al. 2013). Based on the evidence and due to the potential impact of splice donor variants, the p.691+2T>C variant is classified as pathogenic for GBE1-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. (less)
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Pathogenic
(Dec 06, 2018)
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criteria provided, single submitter
Method: clinical testing
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Gbe1 Deficiency
Affected status: yes
Allele origin:
germline
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Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego
Accession: SCV000996223.1
First in ClinVar: Oct 20, 2019 Last updated: Oct 20, 2019 |
Comment:
This variant affects the canonical splice donor site of intron 5 of 15, and is therefore predicted to interfere with splicing and result in loss … (more)
This variant affects the canonical splice donor site of intron 5 of 15, and is therefore predicted to interfere with splicing and result in loss of normal protein function. This variant has been previously reported as a compound heterozygous change in patients with GBE1 glycogen storage disease (PMID: 23218673, 19813197). It is present in the heterozygous state in the gnomAD population database at a frequency of 0.082% (183/223430; max AF: 0.0013 in European populations) and thus is presumed to be rare. Multiple splice prediction tools suggest this variant is likely to interfere with normal splicing. Based on the available evidence, the c.691+2T>C variant is classified as Pathogenic. (less)
Number of individuals with the variant: 1
|
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Pathogenic
(Feb 03, 2020)
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criteria provided, single submitter
Method: clinical testing
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Glycogen storage disease, type IV
Affected status: yes
Allele origin:
unknown
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Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV001366207.2
First in ClinVar: Jul 04, 2020 Last updated: Dec 12, 2020 |
Comment:
This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PM2,PP5.
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Pathogenic
(Jun 16, 2020)
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criteria provided, single submitter
Method: clinical testing
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Glycogen storage disease
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000245614.2
First in ClinVar: Sep 14, 2015 Last updated: May 29, 2021 |
Comment:
The c.691+2T>C variant in GBE1 has been reported in at least 3 compound heterozygous individuals with glycogen storage disease IV and segregated with disease in … (more)
The c.691+2T>C variant in GBE1 has been reported in at least 3 compound heterozygous individuals with glycogen storage disease IV and segregated with disease in at least 2 affected relatives from 1 family (Fernandez 2010 PMID:19813197, Ravenscroft 2013 PMID:23218673, Schene 2018 PMID:30569318). It has also been reported in ClinVar (Variation ID 208584) and has been identified in 0.14% (160/110918) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. This variant occurs within the canonical splice site (+/- 1,2) and is predicted to cause altered splicing leading to an abnormal or absent protein. Loss of function of the GBE1 gene is an established disease mechanism in autosomal recessive glycogen storage disease IV. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive glycogen storage disease IV. ACMG/AMP Criteria applied: PVS1, PM3_Strong, PP1_Moderate. (less)
Number of individuals with the variant: 2
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Pathogenic
(Aug 27, 2021)
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criteria provided, single submitter
Method: clinical testing
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Glycogen storage disease, type IV
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001821399.1
First in ClinVar: Sep 08, 2021 Last updated: Sep 08, 2021 |
Comment:
Variant summary: GBE1 c.691+2T>C is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to … (more)
Variant summary: GBE1 c.691+2T>C is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: four predict the variant abolishes a 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00089 in 193326 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in GBE1 causing Glycogen Storage Disease, Type IV (0.00089 vs 0.0013), allowing no conclusion about variant significance. c.691+2T>C has been reported in the literature in several compound heterozygous individuals affected with Glycogen Storage Disease, Type IV (e.g. Fernandez_2010, Ravenscroft_2013, Bendroth-Asmussen_2016, Schene_2018, Szymanska_2018). These data indicate that the variant is likely to be associated with disease. Several publications also reported severely reduced enzyme activities in patient derived cells (e.g. Fernandez_2010, Ravenscroft_2013, Schene_2018, Szymanska_2018). 13 submitters have provided clinical-significance assessments for this variant in ClinVar after 2014, and all of them classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Feb 04, 2021)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV002050171.1
First in ClinVar: Jan 08, 2022 Last updated: Jan 08, 2022 |
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Pathogenic
(Jan 27, 2022)
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criteria provided, single submitter
Method: curation
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Glycogen storage disease, type IV
(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: SCV002097120.1
First in ClinVar: Feb 13, 2022 Last updated: Feb 13, 2022 |
Comment:
The c.691+2T>C variant in GBE1 has been reported in at least 10 individuals with GBE1-related disorders (PMID: 19813197, 23218673, 25489661, 26166723, 26886200, 28507268, 29379554, 30569318, … (more)
The c.691+2T>C variant in GBE1 has been reported in at least 10 individuals with GBE1-related disorders (PMID: 19813197, 23218673, 25489661, 26166723, 26886200, 28507268, 29379554, 30569318, Akman 2015, Thomsen 2016) and has been identified in 0.1% (160/110918) of European (non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs192044702). Although this variant has been seen in the general population in a heterozygous state, its frequency is not high enough to rule out a pathogenic role. Of the many affected individuals, 1 was a compound heterozygote that carried a reported likely pathogenic variant in trans, and 2 were compound heterozygotes that carried a reported pathogenic variant with unknown phase, which increases the likelihood that the c.691+2T>C variant is pathogenic (Variation ID#: 2777; PMID: 25489661, 28507268, Akman 2015). This variant has also been reported in ClinVar (Variation ID#: 208584) and has been interpreted as pathogenic by multiple submitters. The phenotype of individuals homozygous or compound heterozygous for this variant is highly specific for GBE1-related disorders based on strict biochemical investigations consistent with disease (PMID: 19813197, 23218673). This variant is located in the 3' splice region. Computational tools predict a splicing impact, though this information is not predictive enough to determine pathogenicity. Loss of function of the GBE1 gene is an established disease mechanism in autosomal recessive GBE1-related disorders. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive GBE1-related disorders. ACMG/AMP Criteria applied: PVS1, PM3_strong, PP4 (Richards 2015). (less)
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Pathogenic
(Aug 22, 2022)
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criteria provided, single submitter
Method: clinical testing
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Glycogen storage disease, type IV
Affected status: yes
Allele origin:
germline
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MGZ Medical Genetics Center
Accession: SCV002581805.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022 |
Number of individuals with the variant: 2
Sex: female
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Pathogenic
(Oct 19, 2020)
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criteria provided, single submitter
Method: clinical testing
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Glycogen storage disease, type IV
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
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Victorian Clinical Genetics Services, Murdoch Childrens Research Institute
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002767880.1
First in ClinVar: Dec 24, 2022 Last updated: Dec 24, 2022 |
Comment:
Based on the classification scheme VCGS_Germline_v1.3.3, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism … (more)
Based on the classification scheme VCGS_Germline_v1.3.3, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with glycogen storage disease IV (GSD-IV) (MIM#232500) and adult form polyglucosan body disease (MIM#263570). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0211 - Canonical splice site variant without proven consequence on splicing (no functional evidence available). (SP) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD (v2) <0.01 for a recessive condition (194 heterozygotes, 0 homozygotes). (SP) 0505 - Abnormal splicing is predicted by in silico tools and affected nucleotide is highly conserved. (SP) 0704 - Another splice variant comparable to the one identified in this case has limited previous evidence for pathogenicity. This splice variant (c.691+5G>C) has been reported as pathogenic and in a homozygous patient with GSD-IV (ClinVar, PMID: 17662246). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been reported as pathogenic in multiple patients with either GSD-IV or adult form polyglucosan body disease (LOVD, ClinVar, PMID: 29379554). (SP) 1201 - Heterozygous variant detected in trans with a second likely pathogenic heterozygous variant (p.(Gln236His)) in a recessive disease. (SP) 1205 - This variant has been shown to be maternally inherited (PathWest). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign (less)
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Pathogenic
(May 10, 2022)
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criteria provided, single submitter
Method: clinical testing
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Glycogen storage disease, type IV
Adult polyglucosan body disease
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV000894328.2
First in ClinVar: Mar 31, 2019 Last updated: Dec 31, 2022 |
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Pathogenic
(Jan 27, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000321703.7
First in ClinVar: Oct 09, 2016 Last updated: Mar 04, 2023 |
Comment:
Canonical splice site variant in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: … (more)
Canonical splice site variant in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 23352160, 19813197, 23218673, 25489661, 26166723, 28507268, 30569318, 31980526, 31862442, 29379554, 31589614, 33726816, 32528171, 33332610, 31127727, 32668698, 34426522) (less)
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Pathogenic
(May 27, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Not provided
Affected status: unknown
Allele origin:
germline
|
Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV001713290.3
First in ClinVar: Jun 15, 2021 Last updated: Jun 03, 2023 |
Comment:
PVS1, PS3, PS4_moderate, PP1, PP3
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Pathogenic
(Nov 03, 2021)
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criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: not provided
Allele origin:
germline
|
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden
Accession: SCV002010125.3
First in ClinVar: Nov 06, 2021 Last updated: Jul 16, 2023 |
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Pathogenic
(Sep 13, 2023)
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criteria provided, single submitter
Method: clinical testing
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Glycogen storage disease, type IV
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV003834976.2
First in ClinVar: Mar 11, 2023 Last updated: Dec 24, 2023 |
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Pathogenic
(Nov 21, 2022)
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criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV002024214.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Jan 30, 2024)
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criteria provided, single submitter
Method: clinical testing
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Glycogen storage disease, type IV
Glycogen storage disease IV, classic hepatic
Explanation for multiple conditions: Uncertain.
The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000835705.6
First in ClinVar: Oct 10, 2018 Last updated: Feb 28, 2024 |
Comment:
This sequence change affects a donor splice site in intron 5 of the GBE1 gene. It is expected to disrupt RNA splicing. Variants that disrupt … (more)
This sequence change affects a donor splice site in intron 5 of the GBE1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in GBE1 are known to be pathogenic (PMID: 15452297, 20058079). This variant is present in population databases (rs192044702, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. Disruption of this splice site has been observed in individual(s) with glycogen storage disease type IV (PMID: 19813197, 23218673, 26166723, 30569318). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 208584). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Nov 01, 2023)
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criteria provided, single submitter
Method: clinical testing
|
GBE1-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV004734144.1
First in ClinVar: Mar 16, 2024 Last updated: Mar 16, 2024 |
Comment:
The GBE1 c.691+2T>C variant is predicted to disrupt the GT donor site and interfere with normal splicing. This variant has been reported in the compound … (more)
The GBE1 c.691+2T>C variant is predicted to disrupt the GT donor site and interfere with normal splicing. This variant has been reported in the compound heterozygous state in two presumably unrelated families, one of which included siblings initially diagnosed with lethal multiple pterygium syndrome (Fernandez et al. 2010. PubMed ID: 19813197; Ravenscroft et al. 2013. PubMed ID: 23218673). More recently, this variant was identified in the compound heterozygous state with a second pathogenic GBE1 variant in tissue from a fetus lost in a first trimester miscarriage. Histopathological findings in the fetal tissue were consistent with glycogen storage disease type IV (GSD IV) (Bendroth-Asmussen et al. 2016. PubMed ID: 26166723). At PreventionGenetics, we have observed this variant in combination with a second pathogenic variant in at least two unrelated affected patients. This variant is reported in 0.14% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/3-81698005-A-G). Variants that disrupt the consensus splice donor site in GBE1 are expected to be pathogenic. This variant is interpreted as pathogenic. (less)
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Pathogenic
(Jan 01, 2024)
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criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001248812.20
First in ClinVar: May 09, 2020 Last updated: Apr 15, 2024 |
Comment:
GBE1: PVS1, PM2, PM3
Number of individuals with the variant: 6
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Pathogenic
(Sep 28, 2023)
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criteria provided, single submitter
Method: clinical testing
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Adult polyglucosan body disease
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
unknown
|
Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV004100751.2
First in ClinVar: Nov 04, 2023 Last updated: Apr 15, 2024 |
Comment:
Criteria applied: PVS1,PM3_VSTR,PM2_SUP
Clinical Features:
Leukodystrophy (present) , Dementia (present)
Sex: male
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Pathogenic
(Sep 16, 2020)
|
no assertion criteria provided
Method: clinical testing
|
Glycogen storage disease type IV
Affected status: unknown
Allele origin:
germline
|
Natera, Inc.
Accession: SCV001461486.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
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Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, Amsterdam University Medical Center
Study: VKGL Data-share Consensus
Accession: SCV001808499.1 First in ClinVar: Aug 27, 2021 Last updated: Aug 27, 2021 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001742769.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001932565.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001951658.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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Pathogenic
(-)
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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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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: SCV001969597.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV002036401.1 First in ClinVar: Dec 18, 2021 Last updated: Dec 18, 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 |
---|---|---|---|---|
Precision medicine integrating whole-genome sequencing, comprehensive metabolomics, and advanced imaging. | Hou YC | Proceedings of the National Academy of Sciences of the United States of America | 2020 | PMID: 31980526 |
Glycogen Storage Disease Type IV: A Rare Cause for Neuromuscular Disorders or Often Missed? | Schene IF | JIMD reports | 2019 | PMID: 30569318 |
Variable clinical presentation of glycogen storage disease type IV: from severe hepatosplenomegaly to cardiac insufficiency. Some discrepancies in genetic and biochemical abnormalities. | Szymańska E | Archives of medical science : AMS | 2018 | PMID: 29379554 |
Teaching NeuroImages: Prominent spinal cord atrophy and white matter changes in adult polyglucosan body disease. | López Chiriboga AS | Neurology | 2017 | PMID: 28507268 |
Utility of a next-generation sequencing-based gene panel investigation in German patients with genetically unclassified limb-girdle muscular dystrophy. | Kuhn M | Journal of neurology | 2016 | PMID: 26886200 |
Glycogen Storage Disease Type IV: A Case With Histopathologic Findings in First-Trimester Placental Tissue. | Bendroth-Asmussen L | International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists | 2016 | PMID: 26166723 |
Glycogen Storage Disease Type IV and Early Implantation Defect: Early Trophoblastic Involvement Associated with a New GBE1 Mutation. | Dainese L | Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society | 2016 | PMID: 25489661 |
Rare complete knockouts in humans: population distribution and significant role in autism spectrum disorders. | Lim ET | Neuron | 2013 | PMID: 23352160 |
Whole exome sequencing in foetal akinesia expands the genotype-phenotype spectrum of GBE1 glycogen storage disease mutations. | Ravenscroft G | Neuromuscular disorders : NMD | 2013 | PMID: 23218673 |
Glycogen storage disease type IV: novel mutations and molecular characterization of a heterogeneous disorder. | Li SC | Journal of inherited metabolic disease | 2010 | PMID: 20058079 |
Non-lethal neonatal neuromuscular variant of glycogenosis type IV with novel GBE1 mutations. | Fernandez C | Muscle & nerve | 2010 | PMID: 19813197 |
Null mutations and lethal congenital form of glycogen storage disease type IV. | Assereto S | Biochemical and biophysical research communications | 2007 | PMID: 17662246 |
Splicing in action: assessing disease causing sequence changes. | Baralle D | Journal of medical genetics | 2005 | PMID: 16199547 |
Clinical and genetic heterogeneity of branching enzyme deficiency (glycogenosis type IV). | Bruno C | Neurology | 2004 | PMID: 15452297 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=GBE1 | - | - | - | - |
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Text-mined citations for rs192044702 ...
HelpRecord last updated Apr 20, 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.