rs61731664

Positions:

chr22-31838811-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001242896.3(DEPDC5):c.2481G>A(p.Pro827=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0178 in 1,613,968 control chromosomes in the GnomAD database, including 288 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 16 hom., cov: 32)

Exomes 𝑓: 0.018 ( 272 hom. )

Consequence

DEPDC5
NM_001242896.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.09

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 22-31838811-G-A is Benign according to our data. Variant chr22-31838811-G-A is described in ClinVar as [Benign]. Clinvar id is 238676.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31838811-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.09 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0136 (2065/152186) while in subpopulation SAS AF= 0.0197 (95/4826). AF 95% confidence interval is 0.0176. There are 16 homozygotes in gnomad4. There are 1056 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEPDC5	NM_001242896.3 linkuse as main transcript	c.2481G>A	p.Pro827=	synonymous_variant	27/43	ENST00000651528.2	NP_001229825.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEPDC5	ENST00000651528.2 linkuse as main transcript	c.2481G>A	p.Pro827=	synonymous_variant	27/43		NM_001242896.3	ENSP00000498382	P4	O75140-10

Frequencies

GnomAD3 genomes

AF:

0.0136

AC:

2063

AN:

152068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00311

Gnomad AMI

AF:

0.0198

Gnomad AMR

AF:

0.0145

Gnomad ASJ

AF:

0.00806

Gnomad EAS

AF:

0.00212

Gnomad SAS

AF:

0.0193

Gnomad FIN

AF:

0.0246

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0184

Gnomad OTH

AF:

0.0202

GnomAD3 exomes

AF:

0.0168

AC:

4196

AN:

249442

Hom.:

AF XY:

0.0175

AC XY:

2365

AN XY:

135304

show subpopulations

Gnomad AFR exome

AF:

0.00265

Gnomad AMR exome

AF:

0.0131

Gnomad ASJ exome

AF:

0.0111

Gnomad EAS exome

AF:

0.00250

Gnomad SAS exome

AF:

0.0228

Gnomad FIN exome

AF:

0.0237

Gnomad NFE exome

AF:

0.0195

Gnomad OTH exome

AF:

0.0213

GnomAD4 exome

AF:

0.0183

AC:

26716

AN:

1461782

Hom.:

272

Cov.:

AF XY:

0.0186

AC XY:

13501

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.00227

Gnomad4 AMR exome

AF:

0.0131

Gnomad4 ASJ exome

AF:

0.00953

Gnomad4 EAS exome

AF:

0.00212

Gnomad4 SAS exome

AF:

0.0225

Gnomad4 FIN exome

AF:

0.0245

Gnomad4 NFE exome

AF:

0.0192

Gnomad4 OTH exome

AF:

0.0167

GnomAD4 genome

AF:

0.0136

AC:

2065

AN:

152186

Hom.:

Cov.:

AF XY:

0.0142

AC XY:

1056

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.00310

Gnomad4 AMR

AF:

0.0145

Gnomad4 ASJ

AF:

0.00806

Gnomad4 EAS

AF:

0.00213

Gnomad4 SAS

AF:

0.0197

Gnomad4 FIN

AF:

0.0246

Gnomad4 NFE

AF:

0.0184

Gnomad4 OTH

AF:

0.0200

Alfa

AF:

0.0171

Hom.:

Bravo

AF:

0.0133

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.0209

EpiControl

AF:

0.0208

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	GeneDx	Aug 05, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 07, 2018	- -

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

Apr 27, 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

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.034

DANN

Benign

0.80

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