ClinVar Genomic variation as it relates to human health
NM_152564.5(VPS13B):c.11831_11840del (p.Pro3944fs)
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.11831_11840del (p.Pro3944fs)
Variation ID: 56643 Accession: VCV000056643.7
- Type and length
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Deletion, 10 bp
- Location
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Cytogenetic: 8q22.2 8: 99875502-99875511 (GRCh38) [ NCBI UCSC ] 8: 100887730-100887739 (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 24, 2013 Feb 14, 2024 Jan 28, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_152564.5:c.11831_11840del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_689777.3:p.Pro3944fs frameshift NM_017890.5:c.11906_11915del MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_060360.3:p.Pro3969fs frameshift NM_017890.4:c.11906_11915del10 NM_017890.4:c.11906_11915delCCAGCTGTTC NC_000008.11:g.99875503_99875512del NC_000008.10:g.100887731_100887740del NG_007098.2:g.867238_867247del LRG_351:g.867238_867247del LRG_351t1:c.11906_11915del LRG_351p1:p.Pro3969fs - Protein change
- P3969fs, P3944fs
- Other names
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- Canonical SPDI
- NC_000008.11:99875501:CCCAGCTGTTC:C
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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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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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VPS13B | - | - |
GRCh38 GRCh37 |
5960 | 6030 |
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 (3) |
criteria provided, multiple submitters, no conflicts
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Jan 28, 2024 | RCV000050056.8 |
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
(Jan 28, 2024)
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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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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001583216.4
First in ClinVar: May 10, 2021 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Pro3969Leufs*41) in the VPS13B gene. While this is not anticipated to result in nonsense mediated decay, … (more)
This sequence change creates a premature translational stop signal (p.Pro3969Leufs*41) in the VPS13B gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 54 amino acid(s) of the VPS13B protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with clinical features of Cohen syndrome (PMID: 15141358; externalcommunication). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 56643). This variant disrupts the C-terminus of the VPS13B protein. Other variant(s) that disrupt this region (p.Ser3970Glnfs*22) have been observed in individuals with VPS13B-related conditions (PMID: 16648375). This suggests that this may be a clinically significant region of the protein. For these reasons, this variant has been classified as Pathogenic. (less)
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Likely pathogenic
(Apr 25, 2022)
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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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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000699444.4
First in ClinVar: Jul 24, 2013 Last updated: May 16, 2022 |
Comment:
Variant summary: VPS13B c.11906_11915del10 (p.Pro3969LeufsX41) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: VPS13B c.11906_11915del10 (p.Pro3969LeufsX41) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 251604 control chromosomes (gnomAD). c.11906_11915del10 has been reported in the literature in at-least one compound heterozygous individual affected with Cohen Syndrome (Kolehmainen_2004) and subsequently cited by others (example Seifert_2009, Reuter_2018). These data do not allow firm conclusions about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. A ClinVar submitter (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. (less)
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probable-pathogenic
(-)
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no assertion criteria provided
Method: not provided
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Cohen syndrome
Affected status: not provided
Allele origin:
not provided
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Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)
Accession: SCV000082465.1
First in ClinVar: Jul 24, 2013 Last updated: Jul 24, 2013
Comment:
FinDis database variant: This variant was not found or characterized by our laboratory, data were collected from public sources: see reference
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Comment:
Converted during submission to Likely pathogenic.
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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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The Personal Genome Project Canada: findings from whole genome sequences of the inaugural 56 participants. | Reuter MS | CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne | 2018 | PMID: 29431110 |
Expanded mutational spectrum in Cohen syndrome, tissue expression, and transcript variants of COH1. | Seifert W | Human mutation | 2009 | PMID: 19006247 |
Mutational spectrum of COH1 and clinical heterogeneity in Cohen syndrome. | Seifert W | Journal of medical genetics | 2006 | PMID: 16648375 |
Delineation of Cohen syndrome following a large-scale genotype-phenotype screen. | Kolehmainen J | American journal of human genetics | 2004 | PMID: 15141358 |
Text-mined citations for rs386834069 ...
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.