rs118001924

Positions:

chr22-31843753-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001242896.3(DEPDC5):c.2742G>A(p.Glu914Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0134 in 1,614,024 control chromosomes in the GnomAD database, including 191 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 19 hom., cov: 32)

Exomes 𝑓: 0.014 ( 172 hom. )

Consequence

DEPDC5
NM_001242896.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.08

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 22-31843753-G-A is Benign according to our data. Variant chr22-31843753-G-A is described in ClinVar as [Benign]. Clinvar id is 238677.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31843753-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=3.08 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0116 (1773/152240) while in subpopulation AMR AF= 0.0189 (289/15290). AF 95% confidence interval is 0.0171. There are 19 homozygotes in gnomad4. There are 858 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEPDC5	NM_001242896.3 linkuse as main transcript	c.2742G>A	p.Glu914Glu	synonymous_variant	29/43	ENST00000651528.2	NP_001229825.1	O75140-10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEPDC5	ENST00000651528.2 linkuse as main transcript	c.2742G>A	p.Glu914Glu	synonymous_variant	29/43		NM_001242896.3	ENSP00000498382.1		O75140-10
ENSG00000285404	ENST00000646701.1 linkuse as main transcript	c.1786+24528G>A		intron_variant				ENSP00000496158.1		A0A2R8YF50

Frequencies

GnomAD3 genomes

AF:

0.0117

AC:

1773

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00292

Gnomad AMI

AF:

0.0264

Gnomad AMR

AF:

0.0189

Gnomad ASJ

AF:

0.0236

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0118

Gnomad FIN

AF:

0.00680

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0162

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.0119

AC:

2982

AN:

249572

Hom.:

AF XY:

0.0125

AC XY:

1696

AN XY:

135402

show subpopulations

Gnomad AFR exome

AF:

0.00168

Gnomad AMR exome

AF:

0.00773

Gnomad ASJ exome

AF:

0.0253

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.0122

Gnomad FIN exome

AF:

0.00881

Gnomad NFE exome

AF:

0.0158

Gnomad OTH exome

AF:

0.0137

GnomAD4 exome

AF:

0.0135

AC:

19805

AN:

1461784

Hom.:

172

Cov.:

AF XY:

0.0137

AC XY:

9987

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.00245

Gnomad4 AMR exome

AF:

0.00760

Gnomad4 ASJ exome

AF:

0.0253

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0119

Gnomad4 FIN exome

AF:

0.00973

Gnomad4 NFE exome

AF:

0.0146

Gnomad4 OTH exome

AF:

0.0133

GnomAD4 genome

AF:

0.0116

AC:

1773

AN:

152240

Hom.:

Cov.:

AF XY:

0.0115

AC XY:

858

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.00291

Gnomad4 AMR

AF:

0.0189

Gnomad4 ASJ

AF:

0.0236

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0116

Gnomad4 FIN

AF:

0.00680

Gnomad4 NFE

AF:

0.0162

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.0153

Hom.:

Bravo

AF:

0.0115

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.0176

EpiControl

AF:

0.0186

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	DEPDC5: BP4, BP7, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 25, 2019	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 02, 2016

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Familial focal epilepsy with variable foci

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

7.6

DANN

Benign

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

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

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