ClinVar Genomic variation as it relates to human health
NM_001242896.3(DEPDC5):c.3311C>T (p.Ser1104Leu)
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(6); Benign(1); Likely benign(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001242896.3(DEPDC5):c.3311C>T (p.Ser1104Leu)
Variation ID: 210846 Accession: VCV000210846.25
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 22q12.3 22: 31861414 (GRCh38) [ NCBI UCSC ] 22: 32257400 (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 Oct 5, 2015 May 1, 2024 Jan 28, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001242896.3:c.3311C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001229825.1:p.Ser1104Leu missense NM_001136029.4:c.3284C>T NP_001129501.1:p.Ser1095Leu missense NM_001242897.2:c.3030+3861C>T intron variant NM_001363852.2:c.3264+3861C>T intron variant NM_001363854.2:c.3077C>T NP_001350783.1:p.Ser1026Leu missense NM_001364318.2:c.3311C>T NP_001351247.1:p.Ser1104Leu missense NM_001364319.2:c.3077C>T NP_001351248.1:p.Ser1026Leu missense NM_001364320.2:c.3264+3861C>T intron variant NM_001369901.1:c.3227C>T NP_001356830.1:p.Ser1076Leu missense NM_001369902.1:c.3227C>T NP_001356831.1:p.Ser1076Leu missense NM_001369903.1:c.3237+3861C>T intron variant NM_014662.6:c.3237+3861C>T intron variant NR_146296.2:n.3400C>T non-coding transcript variant NR_157126.2:n.3400C>T non-coding transcript variant NC_000022.11:g.31861414C>T NC_000022.10:g.32257400C>T NG_034067.1:g.112464C>T O75140:p.Ser1104Leu - Protein change
- S1104L, S1076L, S1095L, S1026L
- Other names
- -
- Canonical SPDI
- NC_000022.11:31861413: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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0.00020 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00005
The Genome Aggregation Database (gnomAD) 0.00016
1000 Genomes Project 0.00020
The Genome Aggregation Database (gnomAD), exomes 0.00020
Trans-Omics for Precision Medicine (TOPMed) 0.00020
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00022
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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DEPDC5 | - | - |
GRCh38 GRCh37 |
2270 | 2298 |
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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Uncertain significance (1) |
criteria provided, single submitter
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Feb 19, 2015 | RCV000193474.13 | |
Uncertain significance (5) |
criteria provided, multiple submitters, no conflicts
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May 28, 2019 | RCV000254574.21 | |
Uncertain significance (1) |
criteria provided, single submitter
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Jan 28, 2024 | RCV001034651.13 | |
Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
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Apr 7, 2022 | RCV001668361.12 | |
Likely benign (1) |
criteria provided, single submitter
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Jun 19, 2019 | RCV002317677.9 |
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. |
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Uncertain significance
(Feb 19, 2015)
|
criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV000247184.1
First in ClinVar: Oct 05, 2015 Last updated: Oct 05, 2015 |
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Uncertain significance
(May 28, 2019)
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criteria provided, single submitter
Method: clinical testing
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Epilepsy, familial focal, with variable foci 1
Affected status: unknown
Allele origin:
unknown
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Mendelics
Accession: SCV001141410.1
First in ClinVar: Jan 12, 2020 Last updated: Jan 12, 2020 |
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Uncertain significance
(Apr 19, 2019)
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criteria provided, single submitter
Method: clinical testing
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Epilepsy, familial focal, with variable foci 1
Affected status: yes
Allele origin:
maternal
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Baylor Genetics
Accession: SCV001525504.1
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]. This c.3311C>T (p.S1104L) variant has been previously reported in patients … (more)
This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. This c.3311C>T (p.S1104L) variant has been previously reported in patients with FFEVF1 or paroxysmal kinesigenic dyskinesia [PMID 23542697, 29356177], however, another study found this variant lacks strong segregation support [PMID 28717674] (less)
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Benign
(Jun 25, 2020)
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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: SCV001889294.1
First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021 |
Comment:
This variant is associated with the following publications: (PMID: 31639411, 31594065, 31139143, 30093711, 28717674, 23542697, 29356177, 25366275, 27683934)
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Uncertain significance
(Apr 07, 2022)
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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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Revvity Omics, Revvity
Accession: SCV003834327.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
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Uncertain significance
(Jan 28, 2024)
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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: SCV000546537.10
First in ClinVar: Oct 06, 2016 Last updated: Feb 20, 2024 |
Comment:
This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 1104 of the DEPDC5 protein (p.Ser1104Leu). … (more)
This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 1104 of the DEPDC5 protein (p.Ser1104Leu). This variant is present in population databases (rs79027628, gnomAD 0.03%). This missense change has been observed in individual(s) with clinical features of DEPDC5-related conditions (PMID: 23542697, 29356177, 31139143, 31594065). ClinVar contains an entry for this variant (Variation ID: 210846). 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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Likely benign
(Jun 19, 2019)
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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: SCV000851156.4
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)
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Uncertain significance
(Oct 31, 2018)
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criteria provided, single submitter
Method: clinical testing
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Epilepsy, familial focal, with variable foci 1
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV000895416.1
First in ClinVar: Mar 31, 2019 Last updated: Mar 31, 2019 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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Epilepsy, familial focal, with variable foci 1
Affected status: yes
Allele origin:
unknown
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Service de Génétique Moléculaire, Hôpital Robert Debré
Accession: SCV001432416.1
First in ClinVar: Sep 19, 2020 Last updated: Sep 19, 2020 |
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not provided
(-)
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no classification provided
Method: literature only
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Epilepsy, familial focal, with variable foci 1
Affected status: yes
Allele origin:
germline
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GeneReviews
Accession: SCV000321059.2
First in ClinVar: Oct 06, 2016 Last updated: Oct 01, 2022 |
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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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DEPDC5-Related Epilepsy. | Adam MP | - | 2023 | PMID: 27683934 |
[Clinical and genetic characteristics of focal epilepsy in children caused by GATOR1 complex gene variation]. | Deng J | Zhonghua er ke za zhi = Chinese journal of pediatrics | 2019 | PMID: 31594065 |
The Clinical and Genetic Features of Co-occurring Epilepsy and Autism Spectrum Disorder in Chinese Children. | Long S | Frontiers in neurology | 2019 | PMID: 31139143 |
Proline-rich transmembrane protein 2-negative paroxysmal kinesigenic dyskinesia: Clinical and genetic analyses of 163 patients. | Tian WT | Movement disorders : official journal of the Movement Disorder Society | 2018 | PMID: 29356177 |
ExACtly zero or once: A clinically helpful guide to assessing genetic variants in mild epilepsies. | Bennett CA | Neurology. Genetics | 2017 | PMID: 28717674 |
Mutations in DEPDC5 cause familial focal epilepsy with variable foci. | Dibbens LM | Nature genetics | 2013 | PMID: 23542697 |
Familial mesial temporal lobe epilepsy: a benign epilepsy syndrome showing complex inheritance. | Crompton DE | Brain : a journal of neurology | 2010 | PMID: 20864493 |
Text-mined citations for rs79027628 ...
HelpRecord last updated May 08, 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.