ClinVar Genomic variation as it relates to human health
NM_033305.3(VPS13A):c.775A>G (p.Asn259Asp)
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(3); Likely benign(5)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_033305.3(VPS13A):c.775A>G (p.Asn259Asp)
Variation ID: 367346 Accession: VCV000367346.47
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 9q21.2 9: 77219974 (GRCh38) [ NCBI UCSC ] 9: 79834890 (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 Dec 6, 2016 Apr 15, 2024 Mar 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_033305.3:c.775A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_150648.2:p.Asn259Asp missense NM_001018037.2:c.775A>G NP_001018047.1:p.Asn259Asp missense NM_001018038.3:c.775A>G NP_001018048.1:p.Asn259Asp missense NM_015186.4:c.775A>G NP_056001.1:p.Asn259Asp missense NC_000009.12:g.77219974A>G NC_000009.11:g.79834890A>G NG_008931.1:g.47530A>G - Protein change
- N259D
- Other names
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- Canonical SPDI
- NC_000009.12:77219973:A:G
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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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0.00100 (G)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 0.00100
Trans-Omics for Precision Medicine (TOPMed) 0.00220
The Genome Aggregation Database (gnomAD), exomes 0.00239
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00246
The Genome Aggregation Database (gnomAD) 0.00255
Exome Aggregation Consortium (ExAC) 0.00266
1000 Genomes Project 30x 0.00094
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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VPS13A | - | - |
GRCh38 GRCh37 |
3102 | 3183 |
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 (4) |
criteria provided, conflicting classifications
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Dec 29, 2020 | RCV000287997.12 | |
Conflicting interpretations of pathogenicity (7) |
criteria provided, conflicting classifications
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Mar 1, 2024 | RCV000518625.38 | |
Likely benign (1) |
criteria provided, single submitter
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Sep 16, 2020 | RCV003912582.1 |
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
(Mar 14, 2018)
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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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Athena Diagnostics Inc
Accession: SCV000616260.2
First in ClinVar: Dec 19, 2017 Last updated: Oct 19, 2018 |
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Uncertain significance
(Oct 31, 2018)
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criteria provided, single submitter
Method: clinical testing
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Chorea-acanthocytosis
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV000897528.1
First in ClinVar: Mar 31, 2019 Last updated: Mar 31, 2019 |
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Likely benign
(Jan 13, 2018)
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criteria provided, single submitter
Method: clinical testing
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Chorea-acanthocytosis
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000480739.3
First in ClinVar: Dec 06, 2016 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)
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Uncertain significance
(Dec 29, 2020)
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criteria provided, single submitter
Method: clinical testing
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Chorea-acanthocytosis
Affected status: yes
Allele origin:
paternal
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Baylor Genetics
Accession: SCV001521050.1
First in ClinVar: Mar 22, 2021 Last updated: Mar 22, 2021 |
Comment:
This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
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Likely benign
(Jul 21, 2022)
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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: SCV001820073.3
First in ClinVar: Sep 08, 2021 Last updated: Mar 04, 2023 |
Comment:
See Variant Classification Assertion Criteria.
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Likely benign
(Jan 31, 2024)
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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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Invitae
Accession: SCV001001810.7
First in ClinVar: Dec 17, 2019 Last updated: Feb 20, 2024 |
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Likely benign
(Sep 16, 2020)
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criteria provided, single submitter
Method: clinical testing
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VPS13A-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004741886.1
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
(Mar 01, 2024)
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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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001155654.21
First in ClinVar: Feb 03, 2020 Last updated: Apr 15, 2024 |
Comment:
VPS13A: BP4, BS2
Number of individuals with the variant: 7
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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Chorea-acanthocytosis
Affected status: yes
Allele origin:
germline
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Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV000734704.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
unknown
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Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV001554009.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021 |
Comment:
The VPS13A p.Asn259Asp variant was not identified in the literature nor was it identified in Cosmic. The variant was identified in dbSNP (ID: rs41307461), LOVD … (more)
The VPS13A p.Asn259Asp variant was not identified in the literature nor was it identified in Cosmic. The variant was identified in dbSNP (ID: rs41307461), LOVD 3.0 (classified as likely benign) and in ClinVar (classified as a VUS by Illumina, Athena Diagnostics and Fulgent Genetics and as likely benign by Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen). The variant was also identified in control databases in 705 of 282532 chromosomes (2 homozygous) at a frequency of 0.002495 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: European (non-Finnish) in 567 of 128988 chromosomes (freq: 0.004396), Ashkenazi Jewish in 41 of 10364 chromosomes (freq: 0.003956), Other in 23 of 7206 chromosomes (freq: 0.003192), European (Finnish) in 37 of 25112 chromosomes (freq: 0.001473), African in 18 of 24922 chromosomes (freq: 0.000722) and Latino in 19 of 35392 chromosomes (freq: 0.000537), but not in the East Asian and South Asian populations. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. The p.Asn259 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. (less)
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, Amsterdam University Medical Center
Study: VKGL Data-share Consensus
Accession: SCV001807897.1 First in ClinVar: Aug 25, 2021 Last updated: Aug 25, 2021 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001972993.1 First in ClinVar: Oct 08, 2021 Last updated: Oct 08, 2021 |
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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
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 rs41307461 ...
HelpRecord last updated Apr 15, 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.