ClinVar Genomic variation as it relates to human health
NM_001005741.2(GBA1):c.[880T>G;1342G>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
NM_001005741.2(GBA1):c.[880T>G;1342G>C]
- Other names
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GBA, HIS255GLN AND ASP409HIS
- Functional consequence
- -
- Links
- ClinGen: CA028618
- OMIM: 606463.0047
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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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| GBA1 | - | - |
GRCh38 GRCh38 GRCh37 |
32 | 405 | |
| LOC106627981 | - | - | - |
GRCh38 GRCh38 |
- | 359 |
Conditions - Germline
| Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Pathogenic (1) |
no assertion criteria provided
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Apr 1, 2005 | RCV000004580.12 | |
| Pathogenic (1) |
no assertion criteria provided
|
Apr 1, 2005 | RCV000004581.12 |
Submissions - Germline
| Classification
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The submitted germline classification for each SCV record. (Last evaluated) |
Review status
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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
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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
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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
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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
(Apr 01, 2005)
|
no assertion criteria provided
Method: literature only
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GAUCHER DISEASE, TYPE III
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000024755.2
First in ClinVar: Apr 04, 2013 Last updated: Jun 24, 2017 |
Comment on evidence:
In a 25-month-old girl with an atypical form of neuronopathic Gaucher disease between type II (230900) and type III (231000), Filocamo et al. (2005) identified … (more)
In a 25-month-old girl with an atypical form of neuronopathic Gaucher disease between type II (230900) and type III (231000), Filocamo et al. (2005) identified homozygosity for a complex allele containing 2 GBA mutations in cis: an 882T-G transversion in exon 7 resulting in a his255-to-gln (H255Q) substitution and a 1342G-C transversion in exon 10 resulting in an asp409-to-his (D409H; 606463.0006) substitution. Onset of symptoms occurred at age 5 months with hepatosplenomegaly. A few months later, she developed neurologic features, including spasticity with persistent retroflexion of the neck, convergent strabismus, oculomotor apraxia, and abnormal MRI changes. At age 25 months, she showed slow symptom progression and was able to sit alone, walk with support, and pronounce some words. (less)
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Pathogenic
(Apr 01, 2005)
|
no assertion criteria provided
Method: literature only
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GAUCHER DISEASE, TYPE II
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000024754.2
First in ClinVar: Apr 04, 2013 Last updated: Jun 24, 2017 |
Comment on evidence:
In a 25-month-old girl with an atypical form of neuronopathic Gaucher disease between type II (230900) and type III (231000), Filocamo et al. (2005) identified … (more)
In a 25-month-old girl with an atypical form of neuronopathic Gaucher disease between type II (230900) and type III (231000), Filocamo et al. (2005) identified homozygosity for a complex allele containing 2 GBA mutations in cis: an 882T-G transversion in exon 7 resulting in a his255-to-gln (H255Q) substitution and a 1342G-C transversion in exon 10 resulting in an asp409-to-his (D409H; 606463.0006) substitution. Onset of symptoms occurred at age 5 months with hepatosplenomegaly. A few months later, she developed neurologic features, including spasticity with persistent retroflexion of the neck, convergent strabismus, oculomotor apraxia, and abnormal MRI changes. At age 25 months, she showed slow symptom progression and was able to sit alone, walk with support, and pronounce some words. (less)
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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
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Long-term follow-up of a patient with neonatal form of Gaucher disease. | Gragnaniello V | American journal of medical genetics. Part A | 2023 | PMID: 37009750 |
| Common and Rare Variants in TMEM175 Gene Concur to the Pathogenesis of Parkinson's Disease in Italian Patients. | Palomba NP | Molecular neurobiology | 2023 | PMID: 36609826 |
| Gaucher Disease. | Adam MP | - | 2023 | PMID: 20301446 |
| Gaucher Disease. | Adam MP | - | 2023 | PMID: 20301446 |
| Genetic characterization of the Albanian Gaucher disease patient population. | Cullufi P | JIMD reports | 2020 | PMID: 33473340 |
| The GBA p.G85E mutation in Korean patients with non-neuronopathic Gaucher disease: founder and neuroprotective effects. | Kim YM | Orphanet journal of rare diseases | 2020 | PMID: 33176831 |
| Gaucher disease: Biochemical and molecular findings in 141 patients diagnosed in Greece. | Dimitriou E | Molecular genetics and metabolism reports | 2020 | PMID: 32547927 |
| Gaucher disease type 3c: New patients with unique presentations and review of the literature. | Kurolap A | Molecular genetics and metabolism | 2019 | PMID: 31130326 |
| Two siblings with Gaucher type 3c: different clinical presentations. | Karakoyun M | Journal of pediatric endocrinology & metabolism : JPEM | 2019 | PMID: 31026225 |
| GBA, Gaucher Disease, and Parkinson's Disease: From Genetic to Clinic to New Therapeutic Approaches. | Riboldi GM | Cells | 2019 | PMID: 31010158 |
| Resequencing analysis of five Mendelian genes and the top genes from genome-wide association studies in Parkinson's Disease. | Benitez BA | Molecular neurodegeneration | 2016 | PMID: 27094865 |
| Neonatal Jaundice with Splenomegaly: Not a Common Pick. | Gotti G | Fetal and pediatric pathology | 2016 | PMID: 26847548 |
| Spectrum of GBA mutations in patients with Gaucher disease from Slovakia: identification of five novel mutations. | Mattošová S | The Israel Medical Association journal : IMAJ | 2015 | PMID: 25946768 |
| The clinical management of Type 2 Gaucher disease. | Weiss K | Molecular genetics and metabolism | 2015 | PMID: 25435509 |
| Clinicogenetic study of GBA mutations in patients with familial Parkinson's disease. | Li Y | Neurobiology of aging | 2014 | PMID: 24126159 |
| Glucocerebrosidase mutations in a Serbian Parkinson's disease population. | Kumar KR | European journal of neurology | 2013 | PMID: 22812582 |
| Analysis of the β-glucocerebrosidase gene in Turkish Gaucher disease patients: mutation profile and description of a novel mutant allele. | Karaca E | Journal of pediatric endocrinology & metabolism : JPEM | 2012 | PMID: 23426826 |
| β-Glucocerebrosidase gene mutations in two cohorts of Greek patients with sporadic Parkinson's disease. | Moraitou M | Molecular genetics and metabolism | 2011 | PMID: 21745757 |
| Accumulation and distribution of α-synuclein and ubiquitin in the CNS of Gaucher disease mouse models. | Xu YH | Molecular genetics and metabolism | 2011 | PMID: 21257328 |
| Gaucher disease with communicating hydrocephalus and cardiac involvement. | Cindik N | Clinical cardiology | 2010 | PMID: 19816973 |
| Glucocerebrosidase mutation H255Q appears to be exclusively in cis with D409H: structural implications. | Vithayathil J | Clinical genetics | 2009 | PMID: 19459886 |
| Complete screening for glucocerebrosidase mutations in Parkinson disease patients from Greece. | Kalinderi K | Neuroscience letters | 2009 | PMID: 19383421 |
| Promising results of the chaperone effect caused by imino sugars and aminocyclitol derivatives on mutant glucocerebrosidases causing Gaucher disease. | Sánchez-Ollé G | Blood cells, molecules & diseases | 2009 | PMID: 19167250 |
| Molecular analysis of Turkish Gaucher disease patients: identification of novel mutations in glucocerebrosidase (GBA) gene. | Emre S | European journal of medical genetics | 2008 | PMID: 18586596 |
| Haplotype analysis suggests a single Balkan origin for the Gaucher disease [D409H;H255Q] double mutant allele. | Santamaria R | Human mutation | 2008 | PMID: 18429048 |
| Mutation analysis and genotype/phenotype relationships of Gaucher disease patients in Spain. | Alfonso P | Journal of human genetics | 2007 | PMID: 17427031 |
| Analyses of variant acid beta-glucosidases: effects of Gaucher disease mutations. | Liou B | The Journal of biological chemistry | 2006 | PMID: 16293621 |
| Gaucher disease mouse models: point mutations at the acid beta-glucosidase locus combined with low-level prosaposin expression lead to disease variants. | Sun Y | Journal of lipid research | 2005 | PMID: 16061944 |
| Homozygosity for a non-pseudogene complex glucocerebrosidase allele as cause of an atypical neuronopathic form of Gaucher disease. | Filocamo M | American journal of medical genetics. Part A | 2005 | PMID: 15690354 |
| Homozygosity for a non-pseudogene complex glucocerebrosidase allele as cause of an atypical neuronopathic form of Gaucher disease. | Filocamo M | American journal of medical genetics. Part A | 2005 | PMID: 15690354 |
| Identification and functional characterization of five novel mutant alleles in 58 Italian patients with Gaucher disease type 1. | Miocić S | Human mutation | 2005 | PMID: 15605411 |
| Functional analysis of 13 GBA mutant alleles identified in Gaucher disease patients: Pathogenic changes and "modifier" polymorphisms. | Montfort M | Human mutation | 2004 | PMID: 15146461 |
| Perinatal-lethal Gaucher disease. | Mignot C | American journal of medical genetics. Part A | 2003 | PMID: 12838552 |
| Variant Gaucher disease characterized by dysmorphic features, absence of cardiovascular involvement, laryngospasm, and compound heterozygosity for a novel mutation (D409H/C16S). | Bodamer OA | American journal of medical genetics | 2002 | PMID: 11992489 |
| The identification of eight novel glucocerebrosidase (GBA) mutations in patients with Gaucher disease. | Orvisky E | Human mutation | 2002 | PMID: 11933202 |
| Severe valvular and aortic arch calcification in a patient with Gaucher's disease homozygous for the D409H mutation. | George R | Clinical genetics | 2001 | PMID: 11359469 |
| A new variant neuropathic type of Gaucher's disease characterized by hydrocephalus, corneal opacities, deformed toes, and fibrous thickening of spleen and liver capsules. | Inui K | The Journal of pediatrics | 2001 | PMID: 11148530 |
| Glucocerebrosidase gene mutations in patients with type 2 Gaucher disease. | Stone DL | Human mutation | 2000 | PMID: 10649495 |
| Gaucher disease with oculomotor apraxia and cardiovascular calcification (Gaucher type IIIC). | Bohlega S | Neurology | 2000 | PMID: 10636167 |
| D409H/D409H genotype in Gaucher-like disease. | Uyama E | Journal of medical genetics | 1997 | PMID: 9040001 |
| Unusual expression of Gaucher's disease: cardiovascular calcifications in three sibs homozygous for the D409H mutation. | Chabás A | Journal of medical genetics | 1995 | PMID: 8544197 |
| Gaucher disease in Spanish patients: analysis of eight mutations. | Cormand B | Human mutation | 1995 | PMID: 7627184 |
| Gaucher's disease variant characterised by progressive calcification of heart valves and unique genotype. | Abrahamov A | Lancet (London, England) | 1995 | PMID: 7475546 |
| Glucocerebrosidase mutations in Gaucher disease. | Beutler E | Molecular medicine (Cambridge, Mass.) | 1994 | PMID: 8790604 |
| Analysis of human acid beta-glucosidase by site-directed mutagenesis and heterologous expression. | Grace ME | The Journal of biological chemistry | 1994 | PMID: 8294487 |
| Prevalence of nine mutations among Jewish and non-Jewish Gaucher disease patients. | Horowitz M | American journal of human genetics | 1993 | PMID: 8213821 |
| Hydrocephalus, corneal opacities, deafness, valvular heart disease, deformed toes and leptomeningeal fibrous thickening in adult siblings: a new syndrome associated with beta-glucocerebrosidase deficiency and a mosaic population of storage cells. | Uyama E | Acta neurologica Scandinavica | 1992 | PMID: 1333717 |
| Prevalent and rare mutations among Gaucher patients. | Eyal N | Gene | 1990 | PMID: 2269438 |
| Gaucher disease associated with a unique KpnI restriction site: identification of the amino-acid substitution. | Beutler E | Annals of human genetics | 1990 | PMID: 1974409 |
| Gaucher disease: molecular heterogeneity and phenotype-genotype correlations. | Theophilus B | American journal of human genetics | 1989 | PMID: 2502917 |
| http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=GBA | - | - | - | - |
| http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=GBA | - | - | - | - |
| https://erepo.clinicalgenome.org/evrepo/ui/interpretation/495af518-6b93-4c14-bdcc-cc9acf0e57df | - | - | - | - |
| https://erepo.clinicalgenome.org/evrepo/ui/interpretation/4e34ee62-adac-4732-85ac-b08a66341b05 | - | - | - | - |
| https://www.ncbi.nlm.nih.gov/books/NBK1269/ | - | - | - | - |
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Text-mined citations for this variant ...
HelpRecord last updated Nov 03, 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.