rs373471598

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001242896.3(DEPDC5):c.871+9T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000255 in 1,605,340 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

DEPDC5
NM_001242896.3 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.148

Publications

0 publications found

Variant links:

Genes affected

DEPDC5 (HGNC:18423): (DEP domain containing 5, GATOR1 subcomplex subunit) This gene encodes a member of the IML1 family of proteins involved in G-protein signaling pathways. The mechanistic target of rapamycin complex 1 (mTORC1) pathway regulates cell growth by sensing the availability of nutrients. The protein encoded by this gene is a component of the GATOR1 (GAP activity toward Rags) complex which inhibits the amino acid-sensing branch of the mTORC1 pathway. Mutations in this gene are associated with autosomal dominant familial focal epilepsy with variable foci. A single nucleotide polymorphism in an intron of this gene has been associated with an increased risk of hepatocellular carcinoma in individuals with chronic hepatitis C virus infection. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

DEPDC5 Gene-Disease associations (from GenCC):

epilepsy, familial focal, with variable foci 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Ambry Genetics, Illumina, G2P
focal epilepsy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
autosomal dominant epilepsy with auditory features
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
autosomal dominant nocturnal frontal lobe epilepsy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
familial focal epilepsy with variable foci
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Brugada syndrome
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

DEPDC5 links:

ENSG00000285404 (HGNC:):

ENSG00000285404 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 22-31797712-T-C is Benign according to our data. Variant chr22-31797712-T-C is described in CliVar as Likely_benign. Clinvar id is 534812.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-31797712-T-C is described in CliVar as Likely_benign. Clinvar id is 534812.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-31797712-T-C is described in CliVar as Likely_benign. Clinvar id is 534812.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-31797712-T-C is described in CliVar as Likely_benign. Clinvar id is 534812.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-31797712-T-C is described in CliVar as Likely_benign. Clinvar id is 534812.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-31797712-T-C is described in CliVar as Likely_benign. Clinvar id is 534812.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-31797712-T-C is described in CliVar as Likely_benign. Clinvar id is 534812.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-31797712-T-C is described in CliVar as Likely_benign. Clinvar id is 534812.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-31797712-T-C is described in CliVar as Likely_benign. Clinvar id is 534812.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-31797712-T-C is described in CliVar as Likely_benign. Clinvar id is 534812.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-31797712-T-C is described in CliVar as Likely_benign. Clinvar id is 534812.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-31797712-T-C is described in CliVar as Likely_benign. Clinvar id is 534812.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-31797712-T-C is described in CliVar as Likely_benign. Clinvar id is 534812.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-31797712-T-C is described in CliVar as Likely_benign. Clinvar id is 534812.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-31797712-T-C is described in CliVar as Likely_benign. Clinvar id is 534812.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-31797712-T-C is described in CliVar as Likely_benign. Clinvar id is 534812.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-31797712-T-C is described in CliVar as Likely_benign. Clinvar id is 534812.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-31797712-T-C is described in CliVar as Likely_benign. Clinvar id is 534812.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-31797712-T-C is described in CliVar as Likely_benign. Clinvar id is 534812.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-31797712-T-C is described in CliVar as Likely_benign. Clinvar id is 534812.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-31797712-T-C is described in CliVar as Likely_benign. Clinvar id is 534812.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-31797712-T-C is described in CliVar as Likely_benign. Clinvar id is 534812.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-31797712-T-C is described in CliVar as Likely_benign. Clinvar id is 534812.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-31797712-T-C is described in CliVar as Likely_benign. Clinvar id is 534812.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-31797712-T-C is described in CliVar as Likely_benign. Clinvar id is 534812.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-31797712-T-C is described in CliVar as Likely_benign. Clinvar id is 534812.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-31797712-T-C is described in CliVar as Likely_benign. Clinvar id is 534812.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-31797712-T-C is described in CliVar as Likely_benign. Clinvar id is 534812.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-31797712-T-C is described in CliVar as Likely_benign. Clinvar id is 534812.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-31797712-T-C is described in CliVar as Likely_benign. Clinvar id is 534812.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-31797712-T-C is described in CliVar as Likely_benign. Clinvar id is 534812.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-31797712-T-C is described in CliVar as Likely_benign. Clinvar id is 534812.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-31797712-T-C is described in CliVar as Likely_benign. Clinvar id is 534812.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-31797712-T-C is described in CliVar as Likely_benign. Clinvar id is 534812.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-31797712-T-C is described in CliVar as Likely_benign. Clinvar id is 534812.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-31797712-T-C is described in CliVar as Likely_benign. Clinvar id is 534812.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-31797712-T-C is described in CliVar as Likely_benign. Clinvar id is 534812.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-31797712-T-C is described in CliVar as Likely_benign. Clinvar id is 534812.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-31797712-T-C is described in CliVar as Likely_benign. Clinvar id is 534812.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-31797712-T-C is described in CliVar as Likely_benign. Clinvar id is 534812.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-31797712-T-C is described in CliVar as Likely_benign. Clinvar id is 534812.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-31797712-T-C is described in CliVar as Likely_benign. Clinvar id is 534812.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-31797712-T-C is described in CliVar as Likely_benign. Clinvar id is 534812.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-31797712-T-C is described in CliVar as Likely_benign. Clinvar id is 534812.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-31797712-T-C is described in CliVar as Likely_benign. Clinvar id is 534812.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-31797712-T-C is described in CliVar as Likely_benign. Clinvar id is 534812.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-31797712-T-C is described in CliVar as Likely_benign. Clinvar id is 534812.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-31797712-T-C is described in CliVar as Likely_benign. Clinvar id is 534812.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome4 at 37 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEPDC5	NM_001242896.3 link	c.871+9T>C		intron_variant	Intron 13 of 42	ENST00000651528.2	NP_001229825.1	O75140-10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEPDC5	ENST00000651528.2 link	c.871+9T>C		intron_variant	Intron 13 of 42		NM_001242896.3	ENSP00000498382.1		O75140-10
ENSG00000285404	ENST00000646701.1 link	c.787+9T>C		intron_variant	Intron 11 of 20			ENSP00000496158.1		A0A2R8YF50

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000161

AC:

AN:

248720

AF XY:

0.00000741

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000355

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000255

AC:

AN:

1453220

Hom.:

Cov.:

AF XY:

0.0000235

AC XY:

AN XY:

723606

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33324

American (AMR)

AF:

0.00

AC:

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26060

East Asian (EAS)

AF:

0.00

AC:

AN:

39652

South Asian (SAS)

AF:

0.00

AC:

AN:

86092

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.0000326

AC:

AN:

1104106

Other (OTH)

AF:

0.0000166

AC:

AN:

60130

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152120

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41440

American (AMR)

AF:

0.00

AC:

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000966

Hom.:

Bravo

AF:

0.0000416

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Familial focal epilepsy with variable foci

Benign:1

Oct 22, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

DEPDC5-related disorder

Benign:1

Sep 15, 2022

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

9.4

(source)

DANN

Benign

0.50

PhyloP100

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over