ClinVar Genomic variation as it relates to human health
NM_001032221.6(STXBP1):c.37+2dup
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
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NM_001032221.6(STXBP1):c.37+2dup
Variation ID: 870412 Accession: VCV000870412.3
- Type and length
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Duplication, 1 bp
- Location
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Cytogenetic: 9q34.11 9: 127612441-127612442 (GRCh38) [ NCBI UCSC ] 9: 130374720-130374721 (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 May 4, 2020 Sep 27, 2020 Aug 6, 2020 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001032221.6:c.37+2dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
splice donor NM_003165.6:c.37+2dup MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
splice donor NM_001374306.2:c.37+2dup splice donor NM_001374307.2:c.-101+2dup splice donor NM_001374308.2:c.-196+2dup splice donor NM_001374309.2:c.-6+395dup intron variant NM_001374310.2:c.-196+2dup splice donor NM_001374311.2:c.-101+2dup splice donor NM_001374312.2:c.-108+2dup splice donor NM_001374313.2:c.37+2dup splice donor NM_001374314.1:c.37+2dup splice donor NM_001374315.2:c.37+2dup splice donor NC_000009.12:g.127612442dup NC_000009.11:g.130374721dup NG_016623.1:g.5236dup - Protein change
- Other names
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- Canonical SPDI
- NC_000009.12:127612441:T:TT
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- sequence variant affecting splice donor Sequence Ontology [SO:1000072]
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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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Allele frequency
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The frequency of the allele represented by this VCV record.
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- Links
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 | ||
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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
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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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STXBP1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
1055 | 1146 | |
LOC130002651 | - | - | - | GRCh38 | - | 53 |
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. |
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Pathogenic/Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Aug 6, 2020 | RCV001089985.3 |
Submissions - Germline
Classification
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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
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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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Likely pathogenic
(Jun 09, 2018)
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criteria provided, single submitter
Method: clinical testing
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Developmental and epileptic encephalopathy, 4
Affected status: yes
Allele origin:
de novo
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Victorian Clinical Genetics Services, Murdoch Childrens Research Institute
Accession: SCV001244977.1
First in ClinVar: May 04, 2020 Last updated: May 04, 2020 |
Comment:
A heterozygous duplication variant, NM_003165.3(STXBP1):c.37+2dupT, has been identified in intron 1 of 19 of the STXBP1 gene. This variant alters the conserved splice donor recognition … (more)
A heterozygous duplication variant, NM_003165.3(STXBP1):c.37+2dupT, has been identified in intron 1 of 19 of the STXBP1 gene. This variant alters the conserved splice donor recognition site of intron 1 and is predicted to result in loss of protein function either through truncation or nonsense-mediated decay. Further tesing (RNA studies) is required to confirm splicing is affected. The variant is absent in population databases (gnomAD, dbSNP, 1000G), and has not been previously reported in clinical cases. Several variants in the same splice recognition site have also been shown to cause epileptic encephalopathy (Trump et al., 2016; ClinVar). Analysis of parental samples indicated this variant to be de novo. Based on the information available at the time of curation, this variant has been classified as LIKELY PATHOGENIC. (less)
Number of individuals with the variant: 1
Clinical Features:
Epileptic encephalopathy (present) , Global developmental delay (present) , Dystonia (present)
Secondary finding: no
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Pathogenic
(Aug 06, 2020)
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criteria provided, single submitter
Method: clinical testing
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Developmental and epileptic encephalopathy, 4
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
de novo
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Institute of Molecular Medicine and Oncology, Chongqing Medical University
Accession: SCV001431535.1
First in ClinVar: Sep 27, 2020 Last updated: Sep 27, 2020 |
Comment:
We observed a young female patient with a de novo variant NM_003165.6 c.37+2dup of STXBP1.Her clinical symptoms overlapped with symptoms of STXBP1-E, including seizures, intellectual … (more)
We observed a young female patient with a de novo variant NM_003165.6 c.37+2dup of STXBP1.Her clinical symptoms overlapped with symptoms of STXBP1-E, including seizures, intellectual impairment, and dyskinesia. The variation belonged to a donor site mutation at the splice site, which resulted in haploinsufficiency. Unlike the common single nucleotide variant of STXBP1, splicing mutations can produce truncated proteins and even mRNA degradation. The protein cannot be adequately translated, which has a severe impact on brain development. We believe that this discovery provided additional information about the cause of STXBP1-E. Given that this case is an unreported variation, future genetic counseling for such patients and the exploration of the underlying mechanisms of pathogenesis and subsequent treatment will be critical issues. (less)
Clinical Features:
seizures (present) , dyskinesia (present) , intellectual impairment (present)
Age: 0-9 years
Sex: female
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Germline Functional Evidence
Functional
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The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
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A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter. |
Result
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A brief description of the result of this method for 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
Help
This column includes more information supporting functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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sequence variant affecting splice donor
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Institute of Molecular Medicine and Oncology, Chongqing Medical University
Accession: SCV001431535.1
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Citations for germline classification of this variant
HelpThere are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for rs1838431452 ...
HelpRecord last updated Oct 15, 2023
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.