rs55645350

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001242896.3(DEPDC5):c.2170+11G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0986 in 1,612,072 control chromosomes in the GnomAD database, including 8,457 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 887 hom., cov: 32)

Exomes 𝑓: 0.098 ( 7570 hom. )

Consequence

DEPDC5
NM_001242896.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.838

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 links:

ENSG00000285404 (HGNC:):

ENSG00000285404 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 22-31833991-G-A is Benign according to our data. Variant chr22-31833991-G-A is described in ClinVar as [Benign]. Clinvar id is 257660.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEPDC5	NM_001242896.3 link	c.2170+11G>A		intron_variant	Intron 25 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.2170+11G>A		intron_variant	Intron 25 of 42		NM_001242896.3	ENSP00000498382.1		O75140-10
ENSG00000285404	ENST00000646701.1 link	c.1786+14766G>A		intron_variant	Intron 20 of 20			ENSP00000496158.1		A0A2R8YF50

Frequencies

GnomAD3 genomes

AF:

0.104

AC:

15818

AN:

152040

Hom.:

888

Cov.:

show subpopulations

Gnomad AFR

AF:

0.100

Gnomad AMI

AF:

0.178

Gnomad AMR

AF:

0.146

Gnomad ASJ

AF:

0.102

Gnomad EAS

AF:

0.0364

Gnomad SAS

AF:

0.0455

Gnomad FIN

AF:

0.125

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.102

Gnomad OTH

AF:

0.104

GnomAD3 exomes

AF:

0.104

AC:

25898

AN:

248890

Hom.:

1605

AF XY:

0.0992

AC XY:

13403

AN XY:

135052

show subpopulations

Gnomad AFR exome

AF:

0.0977

Gnomad AMR exome

AF:

0.186

Gnomad ASJ exome

AF:

0.0994

Gnomad EAS exome

AF:

0.0388

Gnomad SAS exome

AF:

0.0509

Gnomad FIN exome

AF:

0.128

Gnomad NFE exome

AF:

0.100

Gnomad OTH exome

AF:

0.104

GnomAD4 exome

AF:

0.0980

AC:

143129

AN:

1459912

Hom.:

7570

Cov.:

AF XY:

0.0962

AC XY:

69856

AN XY:

726382

show subpopulations

Gnomad4 AFR exome

AF:

0.0976

Gnomad4 AMR exome

AF:

0.180

Gnomad4 ASJ exome

AF:

0.103

Gnomad4 EAS exome

AF:

0.0304

Gnomad4 SAS exome

AF:

0.0513

Gnomad4 FIN exome

AF:

0.127

Gnomad4 NFE exome

AF:

0.0996

Gnomad4 OTH exome

AF:

0.0933

GnomAD4 genome

AF:

0.104

AC:

15836

AN:

152160

Hom.:

887

Cov.:

AF XY:

0.103

AC XY:

7670

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.100

Gnomad4 AMR

AF:

0.146

Gnomad4 ASJ

AF:

0.102

Gnomad4 EAS

AF:

0.0365

Gnomad4 SAS

AF:

0.0454

Gnomad4 FIN

AF:

0.125

Gnomad4 NFE

AF:

0.102

Gnomad4 OTH

AF:

0.104

Alfa

AF:

0.100

Hom.:

258

Bravo

AF:

0.108

Asia WGS

AF:

0.0690

AC:

239

AN:

3478

EpiCase

AF:

0.0977

EpiControl

AF:

0.105

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 15, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Familial focal epilepsy with variable foci

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.24

DANN

Benign

0.64

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over