ClinVar Genomic variation as it relates to human health
NM_001242896.3(DEPDC5):c.3272C>T (p.Ala1091Val)
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_001242896.3(DEPDC5):c.3272C>T (p.Ala1091Val)
Variation ID: 407344 Accession: VCV000407344.9
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 22q12.3 22: 31861375 (GRCh38) [ NCBI UCSC ] 22: 32257361 (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 Apr 17, 2017 Feb 14, 2024 Oct 13, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001242896.3:c.3272C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001229825.1:p.Ala1091Val missense NM_001136029.4:c.3245C>T NP_001129501.1:p.Ala1082Val missense NM_001242897.2:c.3030+3822C>T intron variant NM_001363852.2:c.3264+3822C>T intron variant NM_001363854.2:c.3038C>T NP_001350783.1:p.Ala1013Val missense NM_001364318.2:c.3272C>T NP_001351247.1:p.Ala1091Val missense NM_001364319.2:c.3038C>T NP_001351248.1:p.Ala1013Val missense NM_001364320.2:c.3264+3822C>T intron variant NM_001369901.1:c.3188C>T NP_001356830.1:p.Ala1063Val missense NM_001369902.1:c.3188C>T NP_001356831.1:p.Ala1063Val missense NM_001369903.1:c.3237+3822C>T intron variant NM_014662.6:c.3237+3822C>T intron variant NR_146296.2:n.3361C>T non-coding transcript variant NR_157126.2:n.3361C>T non-coding transcript variant NC_000022.11:g.31861375C>T NC_000022.10:g.32257361C>T NG_034067.1:g.112425C>T - Protein change
- A1091V, A1013V, A1063V, A1082V
- Other names
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- Canonical SPDI
- NC_000022.11:31861374:C:T
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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.
Trans-Omics for Precision Medicine (TOPMed) 0.00000
The Genome Aggregation Database (gnomAD) 0.00001
Exome Aggregation Consortium (ExAC) 0.00029
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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DEPDC5 | - | - |
GRCh38 GRCh37 |
2264 | 2292 |
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
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
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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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Uncertain significance (1) |
criteria provided, single submitter
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Oct 13, 2023 | RCV000456738.7 | |
Uncertain significance (1) |
no assertion criteria provided
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Apr 8, 2017 | RCV000786292.1 | |
Uncertain significance (1) |
criteria provided, single submitter
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Sep 28, 2017 | RCV002446802.1 |
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
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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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Uncertain significance
(Oct 13, 2023)
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criteria provided, single submitter
Method: clinical testing
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Familial focal epilepsy with variable foci
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000546507.6
First in ClinVar: Apr 17, 2017 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1091 of the DEPDC5 protein (p.Ala1091Val). … (more)
This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1091 of the DEPDC5 protein (p.Ala1091Val). This variant is present in population databases (rs772812141, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with DEPDC5-related conditions. ClinVar contains an entry for this variant (Variation ID: 407344). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
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Uncertain significance
(Sep 28, 2017)
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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: SCV002611925.1
First in ClinVar: Nov 29, 2022 Last updated: Nov 29, 2022 |
Comment:
The p.A1091V variant (also known as c.3272C>T), located in coding exon 32 of the DEPDC5 gene, results from a C to T substitution at nucleotide … (more)
The p.A1091V variant (also known as c.3272C>T), located in coding exon 32 of the DEPDC5 gene, results from a C to T substitution at nucleotide position 3272. The alanine at codon 1091 is replaced by valine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)
Number of individuals with the variant: 1
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Uncertain significance
(Apr 08, 2017)
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no assertion criteria provided
Method: provider interpretation
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not provided
Affected status: unknown
Allele origin:
germline
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Stanford Center for Inherited Cardiovascular Disease, Stanford University
Accession: SCV000925053.1
First in ClinVar: Jun 30, 2019 Last updated: Jun 30, 2019 |
Comment:
Found in a 14 year-old male with paroxysmal atrial fibrillation. He was tested at Invitae. p.Ala1091Val (c.3272C>T) in exon 33 of the DEPDC5 gene (NM_001242896.1; … (more)
Found in a 14 year-old male with paroxysmal atrial fibrillation. He was tested at Invitae. p.Ala1091Val (c.3272C>T) in exon 33 of the DEPDC5 gene (NM_001242896.1; ENST00000400246.5) Chromosome position 22:32257361 C / T We classify this as a Variant of Uncertain Significance (VUS), concluding that there is not sufficient evidence for its pathogenicity to warrant using it for diagnosis or predictive genetic testing. Of note: The vast majority of Pathogenic variants in DEPDC5 currently listed in ClinVar are truncating (i.e. premature stop codon) and are not missense variants like this one. This variant has not previously been reported in the literature in association with disease. The DEPDC5 gene is associated with autosomal dominant familial focal epilepsy with variable foci (FFEVF) (MedGen UID: 348951). Our patient has no personal history of seizures, but his mother was diagnosed with epilepsy in her early 40s and his grandfather has a diagnosis of epilepsy as well. Mother and son both have a history of SVT, and our patient was diagnosed with paroxysmal atrial fibrillation at age 14. This is a conservative amino acid change, resulting in the replacement of a nonpolar alanine with a nonpolar valine. Alanine at this location is very highly conserved across the vertebrate species we have data for. No nearby missense variants (+/- 10 amino acids) have been listed as Likely Pathogenic or Pathogenic in ClinVar. Invitae reports that algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; Align-GVGD: "Class C0"). In total the variant has been seen in at least 17 out of 90,960 individuals from publicly available population datasets. Specifically, this variant was reported in 15/11,411 individuals of South Asian ancestry, and in 2/36,377 with non-Finnish European ancestry, in the gnomAD database, which includes ~140,000 individuals of European, African, Latino, South Asian, Ashkenazi, and East Asian descent. This may be a low-quality site, given that there are no variant calls for 50,000 participants. There is one non-Finnish European individual with another missense change at this codon: p.Ala1091Asp. The highest allele frequency was 0.066% in South Asians. Overall allele frequency was 0.009%. Our patient’s ancestry is Northern European Caucasian. The phenotype of those individuals is not publicly available. The dataset is comprised of multiple cohorts, some of which were recruited from the general population, others were enriched for common cardiovascular disease. The curators made an effort to exclude individuals with severe pediatric diseases. (less)
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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 rs772812141 ...
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.