ClinVar Genomic variation as it relates to human health
NM_152564.5(VPS13B):c.6865+1G>T
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_152564.5(VPS13B):c.6865+1G>T
Variation ID: 644958 Accession: VCV000644958.15
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 8q22.2 8: 100732781 (GRCh37) [ NCBI UCSC ] 8: 99720553 (GRCh38) [ 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 Aug 14, 2019 Feb 14, 2024 Aug 31, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_152564.5:c.6865+1G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
splice donor NM_017890.5:c.6940+1G>T MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
splice donor NC_000008.11:g.99720553G>T NC_000008.10:g.100732781G>T NG_007098.2:g.712288G>T LRG_351:g.712288G>T LRG_351t1:c.6940+1G>T - Protein change
- Other names
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- Canonical SPDI
- NC_000008.11:99720552:G:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- protein truncation Variation Ontology [VariO:0015]
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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 (T)
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Allele frequency
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The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00003
1000 Genomes Project 30x 0.00016
1000 Genomes Project 0.00020
- 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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VPS13B | - | - |
GRCh38 GRCh37 |
5709 | 5776 |
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 (5) |
criteria provided, multiple submitters, no conflicts
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Aug 31, 2023 | RCV000798963.13 |
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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Pathogenic
(Nov 08, 2021)
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criteria provided, single submitter
Method: clinical testing
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Cohen syndrome
Affected status: unknown
Allele origin:
unknown
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Myriad Genetics, Inc.
Accession: SCV002060123.2
First in ClinVar: Jan 15, 2022 Last updated: Dec 24, 2022 |
Comment:
NM_017890.4(VPS13B):c.6940+1G>T is a canonical splice variant classified as pathogenic in the context of Cohen syndrome. c.6940+1G>T has been observed in cases with relevant disease (PMID: … (more)
NM_017890.4(VPS13B):c.6940+1G>T is a canonical splice variant classified as pathogenic in the context of Cohen syndrome. c.6940+1G>T has been observed in cases with relevant disease (PMID: 29758347, 33025479, 30138938). Functional assessments of this variant are available in the literature (PMID: 33025479). c.6940+1G>T has been observed in population frequency databases (gnomAD: EAS 0.01%). In summary, NM_017890.4(VPS13B):c.6940+1G>T is a canonical splice variant in a gene where loss of function is a known mechanism of disease, is predicted to disrupt protein function, and has been observed more frequently in cases with the relevant disease than in healthy populations. Please note: this variant was assessed in the context of healthy population screening. (less)
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Pathogenic
(Apr 11, 2022)
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criteria provided, single submitter
Method: clinical testing
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Cohen syndrome
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002813412.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Pathogenic
(Aug 31, 2023)
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criteria provided, single submitter
Method: clinical testing
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Cohen syndrome
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000938607.6
First in ClinVar: Aug 14, 2019 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this … (more)
For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 644958). Disruption of this splice site has been observed in individuals with Cohen syndrome (PMID: 29758347, 30138938). This variant is present in population databases (rs202046738, gnomAD 0.006%). This sequence change affects a donor splice site in intron 38 of the VPS13B 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 VPS13B are known to be pathogenic (PMID: 15141358, 16648375, 20461111). (less)
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Pathogenic
(Sep 01, 2020)
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no assertion criteria provided
Method: clinical testing
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Cohen syndrome
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
inherited
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Medical Genetic Department, The Affiliated Hospital of Qingdao University
Accession: SCV001499947.1
First in ClinVar: Mar 14, 2021 Last updated: Mar 14, 2021 |
Age: 0-9 years
Sex: female
Ethnicity/Population group: Chinese
Geographic origin: China
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Pathogenic
(Mar 15, 2020)
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no assertion criteria provided
Method: clinical testing
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Cohen syndrome
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV002082627.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
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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
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 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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protein truncation
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Medical Genetic Department, The Affiliated Hospital of Qingdao University
Accession: SCV001499947.1
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Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Functional Analysis of a Compound Heterozygous Mutation in the VPS13B Gene in a Chinese Pedigree with Cohen Syndrome. | Lou G | Journal of molecular neuroscience : MN | 2021 | PMID: 33025479 |
Genetic Evaluation of 114 Chinese Short Stature Children in the Next Generation Era: a Single Center Study. | Huang Z | Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology | 2018 | PMID: 30138938 |
Gene analysis: A rare gene disease of intellectual deficiency-Cohen syndrome. | Yang C | International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience | 2018 | PMID: 29758347 |
High frequency of COH1 intragenic deletions and duplications detected by MLPA in patients with Cohen syndrome. | Parri V | European journal of human genetics : EJHG | 2010 | PMID: 20461111 |
Mutational spectrum of COH1 and clinical heterogeneity in Cohen syndrome. | Seifert W | Journal of medical genetics | 2006 | PMID: 16648375 |
Splicing in action: assessing disease causing sequence changes. | Baralle D | Journal of medical genetics | 2005 | PMID: 16199547 |
Delineation of Cohen syndrome following a large-scale genotype-phenotype screen. | Kolehmainen J | American journal of human genetics | 2004 | PMID: 15141358 |
- | - | - | - | DOI: 10.1007/s12031-020-01713-6 |
Text-mined citations for rs202046738 ...
HelpRecord last updated Feb 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.