Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001242896.3(DEPDC5):c.885A>G(p.Gln295Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0345 in 1,610,742 control chromosomes in the GnomAD database, including 1,124 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.034 ( 109 hom., cov: 31)

Exomes 𝑓: 0.035 ( 1015 hom. )

Consequence

DEPDC5
NM_001242896.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.0840

Publications

7 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 22-31798595-A-G is Benign according to our data. Variant chr22-31798595-A-G is described in ClinVar as Benign. ClinVar VariationId is 257663.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.084 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0575 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	HGVSp	Effect	Exon Rank	Protein
DEPDC5	NM_001242896.3	MANE Select	c.885A>G	p.Gln295Gln	synonymous	Exon 14 of 43	NP_001229825.1
DEPDC5	NM_001364318.2		c.885A>G	p.Gln295Gln	synonymous	Exon 14 of 43	NP_001351247.1
DEPDC5	NM_001136029.4		c.885A>G	p.Gln295Gln	synonymous	Exon 14 of 43	NP_001129501.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DEPDC5	ENST00000651528.2	MANE Select	c.885A>G	p.Gln295Gln	synonymous	Exon 14 of 43	ENSP00000498382.1
DEPDC5	ENST00000382112.8	TSL:1	c.885A>G	p.Gln295Gln	synonymous	Exon 14 of 43	ENSP00000371546.4
DEPDC5	ENST00000433147.2	TSL:1	c.801A>G	p.Gln267Gln	synonymous	Exon 13 of 42	ENSP00000410544.2

Frequencies

GnomAD3 genomes

AF:

0.0337

AC:

5127

AN:

152160

Hom.:

108

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0241

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0233

Gnomad ASJ

AF:

0.0184

Gnomad EAS

AF:

0.0227

Gnomad SAS

AF:

0.0633

Gnomad FIN

AF:

0.0834

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0342

Gnomad OTH

AF:

0.0344

GnomAD2 exomes

AF:

0.0358

AC:

8907

AN:

249028

AF XY:

0.0378

show subpopulations

Gnomad AFR exome

AF:

0.0269

Gnomad AMR exome

AF:

0.0156

Gnomad ASJ exome

AF:

0.0236

Gnomad EAS exome

AF:

0.0203

Gnomad FIN exome

AF:

0.0768

Gnomad NFE exome

AF:

0.0343

Gnomad OTH exome

AF:

0.0318

GnomAD4 exome

AF:

0.0346

AC:

50446

AN:

1458464

Hom.:

1015

Cov.:

AF XY:

0.0353

AC XY:

25607

AN XY:

725628

show subpopulations

African (AFR)

AF:

0.0256

AC:

854

AN:

33380

American (AMR)

AF:

0.0164

AC:

733

AN:

44608

Ashkenazi Jewish (ASJ)

AF:

0.0254

AC:

661

AN:

26018

East Asian (EAS)

AF:

0.0263

AC:

1043

AN:

39588

South Asian (SAS)

AF:

0.0560

AC:

4822

AN:

86184

European-Finnish (FIN)

AF:

0.0722

AC:

3827

AN:

53042

Middle Eastern (MID)

AF:

0.0341

AC:

196

AN:

5742

European-Non Finnish (NFE)

AF:

0.0327

AC:

36248

AN:

1109764

Other (OTH)

AF:

0.0343

AC:

2062

AN:

60138

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

2192

4385

6577

8770

10962

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1336

2672

4008

5344

6680

<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:

5126

AN:

152278

Hom.:

109

Cov.:

AF XY:

0.0368

AC XY:

2743

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.0241

AC:

1001

AN:

41582

American (AMR)

AF:

0.0232

AC:

355

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.0184

AC:

AN:

3472

East Asian (EAS)

AF:

0.0226

AC:

117

AN:

5176

South Asian (SAS)

AF:

0.0634

AC:

306

AN:

4830

European-Finnish (FIN)

AF:

0.0834

AC:

884

AN:

10602

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0342

AC:

2324

AN:

68026

Other (OTH)

AF:

0.0336

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

238

476

715

953

1191

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:

0.0321

Hom.:

193

Bravo

AF:

0.0275

Asia WGS

AF:

0.0340

AC:

120

AN:

3478

EpiCase

AF:

0.0358

EpiControl

AF:

0.0322

ClinVar

ClinVar submissions as Germline

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)

Inborn genetic diseases (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_noAF

Benign

-0.71

CADD

Benign

6.3

(source)

DANN

Benign

0.50

PhyloP100

0.084

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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.

rs16989495

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over