22-31768804-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001242896.3(DEPDC5):c.364-10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0345 in 1,611,876 control chromosomes in the GnomAD database, including 1,133 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.034 ( 108 hom., cov: 32)

Exomes 𝑓: 0.035 ( 1025 hom. )

Consequence

DEPDC5
NM_001242896.3 intron

Scores

Splicing: ADA: 0.00001226

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.689

Publications

6 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: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 22-31768804-C-T is Benign according to our data. Variant chr22-31768804-C-T is described in ClinVar as Benign. ClinVar VariationId is 257662.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.058 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001242896.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DEPDC5	NM_001242896.3	MANE Select	c.364-10C>T	intron	N/A	NP_001229825.1	O75140-10
DEPDC5	NM_001364318.2		c.364-10C>T	intron	N/A	NP_001351247.1	O75140-10
DEPDC5	NM_001136029.4		c.364-10C>T	intron	N/A	NP_001129501.1	O75140-9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DEPDC5	ENST00000651528.2	MANE Select	c.364-10C>T	intron	N/A	ENSP00000498382.1	O75140-10
DEPDC5	ENST00000382112.8	TSL:1	c.364-10C>T	intron	N/A	ENSP00000371546.4	O75140-10
DEPDC5	ENST00000433147.2	TSL:1	c.280-10C>T	intron	N/A	ENSP00000410544.2	H0Y770

Frequencies

GnomAD3 genomes

AF:

0.0337

AC:

5123

AN:

152082

Hom.:

107

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0240

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0233

Gnomad ASJ

AF:

0.0185

Gnomad EAS

AF:

0.0223

Gnomad SAS

AF:

0.0638

Gnomad FIN

AF:

0.0828

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0343

Gnomad OTH

AF:

0.0345

GnomAD2 exomes

AF:

0.0359

AC:

8910

AN:

248018

AF XY:

0.0379

show subpopulations

Gnomad AFR exome

AF:

0.0270

Gnomad AMR exome

AF:

0.0156

Gnomad ASJ exome

AF:

0.0237

Gnomad EAS exome

AF:

0.0200

Gnomad FIN exome

AF:

0.0771

Gnomad NFE exome

AF:

0.0343

Gnomad OTH exome

AF:

0.0321

GnomAD4 exome

AF:

0.0346

AC:

50460

AN:

1459676

Hom.:

1025

Cov.:

AF XY:

0.0353

AC XY:

25632

AN XY:

726204

show subpopulations

African (AFR)

AF:

0.0256

AC:

857

AN:

33444

American (AMR)

AF:

0.0166

AC:

740

AN:

44534

Ashkenazi Jewish (ASJ)

AF:

0.0257

AC:

670

AN:

26086

East Asian (EAS)

AF:

0.0264

AC:

1045

AN:

39620

South Asian (SAS)

AF:

0.0564

AC:

4847

AN:

85944

European-Finnish (FIN)

AF:

0.0726

AC:

3877

AN:

53384

Middle Eastern (MID)

AF:

0.0340

AC:

196

AN:

5758

European-Non Finnish (NFE)

AF:

0.0326

AC:

36166

AN:

1110622

Other (OTH)

AF:

0.0342

AC:

2062

AN:

60284

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

2019

4038

6056

8075

10094

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1328

2656

3984

5312

6640

<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:

0.0337

AC:

5122

AN:

152200

Hom.:

108

Cov.:

AF XY:

0.0369

AC XY:

2743

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.0240

AC:

996

AN:

41532

American (AMR)

AF:

0.0233

AC:

355

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.0185

AC:

AN:

3468

East Asian (EAS)

AF:

0.0222

AC:

115

AN:

5180

South Asian (SAS)

AF:

0.0638

AC:

308

AN:

4824

European-Finnish (FIN)

AF:

0.0828

AC:

877

AN:

10594

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0343

AC:

2332

AN:

68022

Other (OTH)

AF:

0.0337

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

259

519

778

1038

1297

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

204

272

340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0283

Hom.:

Bravo

AF:

0.0275

Asia WGS

AF:

0.0340

AC:

121

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Familial focal epilepsy with variable foci (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.1

(source)

DANN

Benign

0.26

PhyloP100

-0.69

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000012

dbscSNV1_RF

Benign

0.0060

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over