NM_001242896.3(DEPDC5):c.3311C>T (p.Ser1104Leu) AND Epilepsy, familial focal, with variable foci 1

Germline classification:: Uncertain significance (5 submissions)
Last evaluated:: May 28, 2019
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000254574.21

Allele description [Variation Report for NM_001242896.3(DEPDC5):c.3311C>T (p.Ser1104Leu)]

NM_001242896.3(DEPDC5):c.3311C>T (p.Ser1104Leu)

Gene:

DEPDC5:DEP domain containing 5, GATOR1 subcomplex subunit [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

22q12.3

Genomic location:

Preferred name:

NM_001242896.3(DEPDC5):c.3311C>T (p.Ser1104Leu)

HGVS:

NC_000022.11:g.31861414C>T
NG_034067.1:g.112464C>T
NM_001136029.4:c.3284C>T
NM_001242896.3:c.3311C>TMANE SELECT
NM_001242897.2:c.3030+3861C>T
NM_001363852.2:c.3264+3861C>T
NM_001363854.2:c.3077C>T
NM_001364318.2:c.3311C>T
NM_001364319.2:c.3077C>T
NM_001364320.2:c.3264+3861C>T
NM_001369901.1:c.3227C>T
NM_001369902.1:c.3227C>T
NM_001369903.1:c.3237+3861C>T
NM_014662.6:c.3237+3861C>T
NP_001129501.1:p.Ser1095Leu
NP_001229825.1:p.Ser1104Leu
NP_001229825.1:p.Ser1104Leu
NP_001350783.1:p.Ser1026Leu
NP_001351247.1:p.Ser1104Leu
NP_001351248.1:p.Ser1026Leu
NP_001356830.1:p.Ser1076Leu
NP_001356831.1:p.Ser1076Leu
NC_000022.10:g.32257400C>T
NM_001242896.1:c.3311C>T
NR_146296.2:n.3400C>T
NR_157126.2:n.3400C>T
O75140:p.Ser1104Leu

Protein change:

S1026L

Links:

UniProtKB: O75140#VAR_069266; dbSNP: rs79027628

NCBI 1000 Genomes Browser:

rs79027628

Molecular consequence:

NM_001242897.2:c.3030+3861C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001363852.2:c.3264+3861C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001364320.2:c.3264+3861C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001369903.1:c.3237+3861C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_014662.6:c.3237+3861C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001136029.4:c.3284C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001242896.3:c.3311C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001363854.2:c.3077C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001364318.2:c.3311C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001364319.2:c.3077C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001369901.1:c.3227C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001369902.1:c.3227C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_146296.2:n.3400C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_157126.2:n.3400C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

Name:: Epilepsy, familial focal, with variable foci 1 (FFEVF1)
Identifiers:: MONDO: MONDO:0024556; MedGen: C4551983; OMIM: 604364

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000321059	GeneReviews	no classification provided	not provided	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000895416	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Oct 31, 2018)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001141410	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2017)	Uncertain significance (May 28, 2019)	unknown	clinical testing	Citation Link,
SCV001432416	Service de Génétique Moléculaire, Hôpital Robert Debré	no assertion criteria provided	Likely benign	unknown	clinical testing
SCV001525504	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Apr 19, 2019)	maternal	clinical testing	PubMed (4) [See all records that cite these PMIDs] 23542697, 29356177, 28717674, 25741868

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	maternal	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	literature only
not provided	unknown	yes	not provided	1	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in DEPDC5 cause familial focal epilepsy with variable foci.

Dibbens LM, de Vries B, Donatello S, Heron SE, Hodgson BL, Chintawar S, Crompton DE, Hughes JN, Bellows ST, Klein KM, Callenbach PM, Corbett MA, Gardner AE, Kivity S, Iona X, Regan BM, Weller CM, Crimmins D, O'Brien TJ, Guerrero-López R, Mulley JC, Dubeau F, et al.

Nat Genet. 2013 May;45(5):546-51. doi: 10.1038/ng.2599. Epub 2013 Mar 31.

PubMed [citation]

PMID:: 23542697

Proline-rich transmembrane protein 2-negative paroxysmal kinesigenic dyskinesia: Clinical and genetic analyses of 163 patients.

Tian WT, Huang XJ, Mao X, Liu Q, Liu XL, Zeng S, Guo XN, Shen JY, Xu YQ, Tang HD, Yin XM, Zhang M, Tang WG, Liu XR, Tang BS, Chen SD, Cao L.

Mov Disord. 2018 Mar;33(3):459-467. doi: 10.1002/mds.27274. Epub 2018 Jan 22.

PubMed [citation]

PMID:: 29356177

See all PubMed Citations (4)

PMC

Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL.

Genetics in medicine : official journal of the American College of Medical Genetics. 2015 Mar 5; 17(5): 405-424

PMC [article]

PMCID:: PMC4544753
PMID:: 25741868
DOI:: 10.1038/gim.2015.30

Details of each submission

From GeneReviews, SCV000321059.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Fulgent Genetics, Fulgent Genetics, SCV000895416.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Mendelics, SCV001141410.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Service de Génétique Moléculaire, Hôpital Robert Debré, SCV001432416.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		not provided	not provided	1	not provided

From Baylor Genetics, SCV001525504.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

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]

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	maternal	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 19, 2024

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