ClinVar Genomic variation as it relates to human health
NM_152564.5(VPS13B):c.7678G>A (p.Glu2560Lys)
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
-
NM_152564.5(VPS13B):c.7678G>A (p.Glu2560Lys)
Variation ID: 95867 Accession: VCV000095867.51
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 8q22.2 8: 99778930 (GRCh38) [ NCBI UCSC ] 8: 100791158 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Oct 2, 2016 May 12, 2024 Apr 1, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_152564.5:c.7678G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_689777.3:p.Glu2560Lys missense NM_017890.5:c.7753G>A MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_060360.3:p.Glu2585Lys missense NC_000008.11:g.99778930G>A NC_000008.10:g.100791158G>A NG_007098.2:g.770665G>A LRG_351:g.770665G>A LRG_351t1:c.7753G>A LRG_351p1:p.Glu2585Lys LRG_351t2:c.7678G>A LRG_351p2:p.Glu2560Lys - Protein change
- E2560K
- Other names
- -
- Canonical SPDI
- NC_000008.11:99778929:G:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
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.
-
0.00160 (A)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 30x 0.00156
1000 Genomes Project 0.00160
The Genome Aggregation Database (gnomAD) 0.00304
Exome Aggregation Consortium (ExAC) 0.00323
The Genome Aggregation Database (gnomAD), exomes 0.00326
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00346
Trans-Omics for Precision Medicine (TOPMed) 0.00372
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 | ||
---|---|---|---|---|---|---|
HI score
Help
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. |
|||
VPS13B | - | - |
GRCh38 GRCh37 |
5709 | 5776 |
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. |
---|---|---|---|---|
Benign/Likely benign (6) |
criteria provided, multiple submitters, no conflicts
|
Dec 28, 2023 | RCV000081914.29 | |
Likely benign (6) |
criteria provided, multiple submitters, no conflicts
|
Apr 1, 2024 | RCV000513903.21 | |
Benign/Likely benign (6) |
criteria provided, multiple submitters, no conflicts
|
Feb 1, 2024 | RCV000547888.30 | |
Benign (1) |
criteria provided, single submitter
|
Dec 12, 2023 | RCV001199598.10 | |
Likely benign (1) |
criteria provided, single submitter
|
May 6, 2019 | RCV002313810.9 |
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. |
|
---|---|---|---|---|---|
Likely benign
(Dec 09, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: no
Allele origin:
germline
|
Genetic Services Laboratory, University of Chicago
Accession: SCV000249420.2
First in ClinVar: Oct 05, 2015 Last updated: Nov 10, 2017 |
|
|
Likely benign
(May 11, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000512679.4
First in ClinVar: Mar 08, 2017 Last updated: Nov 10, 2017 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
|
|
Likely benign
(Dec 11, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Athena Diagnostics
Accession: SCV000841644.1
First in ClinVar: Nov 05, 2017 Last updated: Nov 05, 2017 |
|
|
Benign
(Oct 11, 2012)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000113849.8
First in ClinVar: Jan 17, 2014 Last updated: May 03, 2018 |
Number of individuals with the variant: 1
Sex: mixed
|
|
Likely benign
(Jan 12, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Cohen syndrome
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV001324016.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. (less)
|
|
Benign
(Feb 14, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV003844718.1
First in ClinVar: Mar 26, 2023 Last updated: Mar 26, 2023 |
Comment:
Variant summary: VPS13B c.7753G>A (p.Glu2585Lys) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign … (more)
Variant summary: VPS13B c.7753G>A (p.Glu2585Lys) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0033 in 250916 control chromosomes in the gnomAD database, including 3 homozygotes. The observed variant frequency is higher than the estimated maximal expected allele frequency for a pathogenic variant in VPS13B causing Cohen Syndrome phenotype (0.0025), strongly suggesting that the variant is benign. Eleven clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments (pathogenic n=1, VUS n=1, benign/likely benign n=9). Based on the evidence outlined above, the variant was classified as benign. (less)
|
|
Benign
(Feb 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Cohen syndrome
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000630887.7
First in ClinVar: Dec 26, 2017 Last updated: Feb 20, 2024 |
|
|
Likely benign
(May 04, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Cohen syndrome
Affected status: no
Allele origin:
germline
|
Molecular Genetics, Royal Melbourne Hospital
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV004812762.1
First in ClinVar: Apr 15, 2024 Last updated: Apr 15, 2024 |
Comment:
European Non-Finnish population allele frequency is 0.5105% (rs111751379, 680/128770 alleles, 3 homozygotes in gnomAD v2.1). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.5.1, … (more)
European Non-Finnish population allele frequency is 0.5105% (rs111751379, 680/128770 alleles, 3 homozygotes in gnomAD v2.1). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.5.1, this variant is classified as LIKELY BENIGN. Following criteria are met: BS1 (less)
|
|
Likely benign
(May 06, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Inborn genetic diseases
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000848643.5
First in ClinVar: Nov 08, 2018 Last updated: May 01, 2024 |
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more)
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
|
|
Likely benign
(Apr 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV004158266.5
First in ClinVar: Nov 20, 2023 Last updated: May 12, 2024 |
Comment:
VPS13B: BP4, BS2
Number of individuals with the variant: 18
|
|
Likely benign
(-)
|
criteria provided, single submitter
Method: clinical testing
|
NOT SPECIFIED
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV000316202.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
|
|
Likely benign
(Mar 17, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: not provided
Allele origin:
germline
|
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics
Accession: SCV000611049.1
First in ClinVar: Nov 05, 2017 Last updated: Nov 05, 2017 |
|
|
Likely benign
(May 18, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Cohen syndrome
Affected status: no
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV001653379.1
First in ClinVar: Jun 08, 2021 Last updated: Jun 08, 2021 |
Sex: mixed
|
|
Benign
(Dec 04, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Cohen syndrome
Affected status: unknown
Allele origin:
germline
|
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago
Accession: SCV000899085.3
First in ClinVar: Apr 25, 2019 Last updated: Dec 09, 2023 |
|
|
Benign
(Dec 12, 2023)
|
criteria provided, single submitter
Method: research
|
Retinitis pigmentosa
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
|
Molecular Genetics Laboratory, Institute for Ophthalmic Research
Accession: SCV001162769.2
First in ClinVar: Jul 16, 2020 Last updated: Dec 17, 2023 |
|
|
Likely Benign
(Dec 28, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV004847402.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024 |
Comment:
The p.Glu2585Lys variant in VPS13B is classified as likely benign because it has been identified in 0.5% (341/68030) of European chromosomes by gnomAD including 4 … (more)
The p.Glu2585Lys variant in VPS13B is classified as likely benign because it has been identified in 0.5% (341/68030) of European chromosomes by gnomAD including 4 homozygotes (http://gnomad.broadinstitute.org, v.3.1.2), which is higher than the expected frequency of a disease cuasing variant in this gene. In addition, computational prediction tools predict that this variant does not impact the protein. ACMG/AMP Criteria applied: BS1, BP4. (less)
|
|
Likely benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Study: VKGL Data-share Consensus
Accession: SCV001798786.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021 |
|
|
Likely benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001918522.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
|
|
Likely benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001932502.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
|
|
Benign
(Dec 20, 2019)
|
no assertion criteria provided
Method: clinical testing
|
Cohen syndrome
Affected status: unknown
Allele origin:
germline
|
Natera, Inc.
Accession: SCV002082654.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
|
|
click to load more click to collapse |
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 |
---|---|---|---|---|
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=VPS13B | - | - | - | - |
Text-mined citations for rs111751379 ...
HelpRecord last updated May 27, 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.