ClinVar Genomic variation as it relates to human health
NM_152564.5(VPS13B):c.11750_11752dup (p.Asp3917dup)
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.
Uncertain significance(5); Likely benign(3)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_152564.5(VPS13B):c.11750_11752dup (p.Asp3917dup)
Variation ID: 56642 Accession: VCV000056642.57
- Type and length
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Duplication, 3 bp
- Location
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Cytogenetic: 8q22.2 8: 99875420-99875421 (GRCh38) [ NCBI UCSC ] 8: 100887648-100887649 (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 Mar 16, 2024 Jan 31, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_152564.5:c.11750_11752dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_689777.3:p.Asp3917dup inframe insertion NM_017890.5:c.11825_11827dup MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_060360.3:p.Asp3942dup inframe insertion NM_017890.4:c.11825_11827dupATG NM_152564.4:c.11750_11752dupATG NC_000008.11:g.99875422_99875424dup NC_000008.10:g.100887650_100887652dup NG_007098.2:g.867157_867159dup LRG_351:g.867157_867159dup LRG_351t1:c.11825_11827dup LRG_351p1:p.Asp3942dup LRG_351t2:c.11750_11752dup - Protein change
- Other names
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- Canonical SPDI
- NC_000008.11:99875420:GATG:GATGATG
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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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0.00220 (GATGATG)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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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
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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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VPS13B | - | - |
GRCh38 GRCh37 |
5686 | 5753 |
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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Conflicting interpretations of pathogenicity (5) |
criteria provided, conflicting classifications
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Jan 31, 2024 | RCV000050055.24 | |
Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
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Feb 26, 2021 | RCV000081876.18 | |
Uncertain significance (1) |
criteria provided, single submitter
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Dec 7, 2018 | RCV002313737.8 | |
Likely benign (1) |
criteria provided, single submitter
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Mar 18, 2022 | RCV003982870.1 |
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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Uncertain significance
(Oct 04, 2013)
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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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Eurofins Ntd Llc (ga)
Accession: SCV000113811.5
First in ClinVar: Jan 17, 2014 Last updated: Aug 02, 2015 |
Number of individuals with the variant: 1
Sex: mixed
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Uncertain significance
(May 28, 2019)
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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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Mendelics
Accession: SCV001137692.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
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Uncertain significance
(Dec 07, 2018)
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criteria provided, single submitter
Method: clinical testing
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Inborn genetic diseases
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000848670.4
First in ClinVar: Nov 12, 2018 Last updated: Nov 29, 2022 |
Comment:
The c.11825_11827dupATG variant (also known as p.D3942dup), located in coding exon 61 of the VPS13B gene, results from an in-frame duplication of ATG at nucleotide … (more)
The c.11825_11827dupATG variant (also known as p.D3942dup), located in coding exon 61 of the VPS13B gene, results from an in-frame duplication of ATG at nucleotide positions 11825 to 11827. This results in the duplication of an aspartate residue between codons 3942 and 3943. This duplication (reported as p.D3942_G3943insD) was detected in compound heterozygous state with a gross deletion encompassing exons 1 to 17 of VPS13B and exon 4 of ORS2 in a patient with developmental delay and cardiac defect (Rivera-Brugués N et al. J. Med. Genet., 2011 Feb;48:136-40). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be neutral by PROVEAN in silico analysis (Choi Y et al., PLoS ONE 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. (less)
Number of individuals with the variant: 1
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Uncertain significance
(Aug 06, 2019)
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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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Revvity Omics, Revvity
Accession: SCV003820436.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
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Likely benign
(Jan 31, 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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Invitae
Accession: SCV000963968.7
First in ClinVar: Aug 14, 2019 Last updated: Feb 20, 2024 |
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Likely benign
(Mar 18, 2022)
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criteria provided, single submitter
Method: clinical testing
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VPS13B-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004799517.1
First in ClinVar: Mar 16, 2024 Last updated: Mar 16, 2024 |
Comment:
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
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Likely benign
(Feb 26, 2021)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV001819828.1
First in ClinVar: Sep 08, 2021 Last updated: Sep 08, 2021 |
Comment:
In-frame insertion of one amino acid in a non-repeat region; Reported previously using alternate nomenclature (c.1827_11828insATG) in an individual with developmental delay, cardiac defects, and … (more)
In-frame insertion of one amino acid in a non-repeat region; Reported previously using alternate nomenclature (c.1827_11828insATG) in an individual with developmental delay, cardiac defects, and dysmorphic features who harbored a partial gene deletion on the opposite allele (in trans) (Rivera-Brugues et al., 2011); This variant is associated with the following publications: (PMID: 20921020) (less)
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Uncertain significance
(Sep 17, 2021)
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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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Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago
Accession: SCV000899088.2
First in ClinVar: Apr 25, 2019 Last updated: May 06, 2023 |
Comment:
VPS13B NM_017890.4 exon 62 p.Asp3942_dup (c.11825_11827dupATG): This variant has been reported in the literature as a compound heterozygote (in trans with a multi-exon deletion of … (more)
VPS13B NM_017890.4 exon 62 p.Asp3942_dup (c.11825_11827dupATG): This variant has been reported in the literature as a compound heterozygote (in trans with a multi-exon deletion of this gene) in 1 individual with a diagnosis of Cohen syndrome (Rivera-Brugues 2011 PMID:20921020, gene identified as alternate name COH1). However, this variant is present in 0.4% (100/24024) of African alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs558633643). This variant is present in ClinVar (Variation ID:56642). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. This variant represents a duplication of 1 amino acid at position 3942 and is not predicted to alter the reading frame. However, the effect of this variant on the protein is unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. (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: SCV000082464.1
First in ClinVar: Jul 24, 2013 Last updated: Jul 24, 2013 |
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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Cohen syndrome diagnosis using whole genome arrays. | Rivera-Brugués N | Journal of medical genetics | 2011 | PMID: 20921020 |
Text-mined citations for rs386834068 ...
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.