22-31833945-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.2135C>T(p.Ser712Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00611 in 1,610,442 control chromosomes in the GnomAD database, including 256 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 115 hom., cov: 32)

Exomes 𝑓: 0.0044 ( 141 hom. )

Consequence

DEPDC5
NM_001242896.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts P:1B:6

Conservation

PhyloP100: 4.70

Publications

10 publications found

Variant links:

COSMIC-nc: COSV56708404

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021339655).

BP6

Variant 22-31833945-C-T is Benign according to our data. Variant chr22-31833945-C-T is described in ClinVar as Benign. ClinVar VariationId is 414462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0704 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.2135C>T	p.Ser712Phe	missense	Exon 25 of 43	NP_001229825.1
DEPDC5	NM_001364318.2		c.2135C>T	p.Ser712Phe	missense	Exon 25 of 43	NP_001351247.1
DEPDC5	NM_001136029.4		c.2135C>T	p.Ser712Phe	missense	Exon 25 of 43	NP_001129501.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DEPDC5	ENST00000651528.2	MANE Select	c.2135C>T	p.Ser712Phe	missense	Exon 25 of 43	ENSP00000498382.1
DEPDC5	ENST00000382112.8	TSL:1	c.2135C>T	p.Ser712Phe	missense	Exon 25 of 43	ENSP00000371546.4
DEPDC5	ENST00000433147.2	TSL:1	c.2051C>T	p.Ser684Phe	missense	Exon 24 of 42	ENSP00000410544.2

Frequencies

GnomAD3 genomes

AF:

0.0226

AC:

3432

AN:

152062

Hom.:

117

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0726

Gnomad AMI

AF:

0.0165

Gnomad AMR

AF:

0.00910

Gnomad ASJ

AF:

0.00374

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0143

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00228

Gnomad OTH

AF:

0.0148

GnomAD2 exomes

AF:

0.00866

AC:

2139

AN:

247084

AF XY:

0.00793

show subpopulations

Gnomad AFR exome

AF:

0.0754

Gnomad AMR exome

AF:

0.00649

Gnomad ASJ exome

AF:

0.00458

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00245

Gnomad OTH exome

AF:

0.00503

GnomAD4 exome

AF:

0.00438

AC:

6394

AN:

1458262

Hom.:

141

Cov.:

AF XY:

0.00460

AC XY:

3334

AN XY:

725466

show subpopulations

African (AFR)

AF:

0.0771

AC:

2572

AN:

33338

American (AMR)

AF:

0.00661

AC:

292

AN:

44206

Ashkenazi Jewish (ASJ)

AF:

0.00410

AC:

106

AN:

25842

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39670

South Asian (SAS)

AF:

0.0130

AC:

1114

AN:

85794

European-Finnish (FIN)

AF:

0.0000938

AC:

AN:

53316

Middle Eastern (MID)

AF:

0.0209

AC:

120

AN:

5738

European-Non Finnish (NFE)

AF:

0.00157

AC:

1747

AN:

1110138

Other (OTH)

AF:

0.00724

AC:

436

AN:

60220

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

266

532

798

1064

1330

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

124

248

372

496

620

<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:

0.0226

AC:

3442

AN:

152180

Hom.:

115

Cov.:

AF XY:

0.0227

AC XY:

1692

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.0726

AC:

3012

AN:

41482

American (AMR)

AF:

0.00909

AC:

139

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00374

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5180

South Asian (SAS)

AF:

0.0145

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10586

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00228

AC:

155

AN:

68026

Other (OTH)

AF:

0.0147

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

162

324

487

649

811

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<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:

0.00851

Hom.:

154

Bravo

AF:

0.0247

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.0686

AC:

257

ESP6500EA

AF:

0.00268

AC:

ExAC

AF:

0.00955

AC:

1154

Asia WGS

AF:

0.00837

AC:

AN:

3478

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)

Focal epilepsy (1)

Inborn genetic diseases (1)

not specified (1)

Self-limited epilepsy with centrotemporal spikes (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.030

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.96

MetaRNN

Benign

0.0021

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

PhyloP100

4.7

PrimateAI

Uncertain

0.48

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.094

Sift

Uncertain

0.014

Sift4G

Uncertain

0.041

Polyphen

0.96

Vest4

0.59

MVP

0.18

MPC

0.76

ClinPred

0.047

GERP RS

4.4

Varity_R

0.27

Mutation Taster

=94/6

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.

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