dbSNP rs566255762: DEPDC5:c.*14_*15insAGGGTTAGAAGGCTGCACC (chr22-31906501-C-CAGGCTGCACCAGGGTTAGA) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_001242896.3(DEPDC5):c.*14_*15insAGGGTTAGAAGGCTGCACC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0187 in 1,612,724 control chromosomes in the GnomAD database, including 322 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 19 hom., cov: 32)

Exomes 𝑓: 0.019 ( 303 hom. )

Consequence

DEPDC5
NM_001242896.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.30

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 -16 ACMG points.

BP6

Variant 22-31906501-C-CAGGCTGCACCAGGGTTAGA is Benign according to our data. Variant chr22-31906501-C-CAGGCTGCACCAGGGTTAGA is described in ClinVar as [Benign]. Clinvar id is 257656.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0143 (2181/152360) while in subpopulation SAS AF= 0.0207 (100/4822). AF 95% confidence interval is 0.0182. There are 19 homozygotes in gnomad4. There are 1115 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 rank	MANE	Protein	UniProt
DEPDC5	NM_001242896.3 link	c.14_15insAGGGTTAGAAGGCTGCACC		3_prime_UTR_variant	Exon 43 of 43	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.14_15insAGGGTTAGAAGGCTGCACC		3_prime_UTR_variant	Exon 43 of 43		NM_001242896.3	ENSP00000498382.1		O75140-10
ENSG00000285404	ENST00000646701.1 link	c.1787-49628_1787-49627insAGGGTTAGAAGGCTGCACC		intron_variant	Intron 20 of 20			ENSP00000496158.1		A0A2R8YF50

Frequencies

GnomAD3 genomes

AF:

0.0143

AC:

2177

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00338

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.0160

Gnomad ASJ

AF:

0.00806

Gnomad EAS

AF:

0.00442

Gnomad SAS

AF:

0.0203

Gnomad FIN

AF:

0.0249

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0191

Gnomad OTH

AF:

0.0248

GnomAD3 exomes

AF:

0.0176

AC:

4368

AN:

247912

Hom.:

AF XY:

0.0184

AC XY:

2483

AN XY:

134868

show subpopulations

Gnomad AFR exome

AF:

0.00209

Gnomad AMR exome

AF:

0.0139

Gnomad ASJ exome

AF:

0.0112

Gnomad EAS exome

AF:

0.00423

Gnomad SAS exome

AF:

0.0262

Gnomad FIN exome

AF:

0.0234

Gnomad NFE exome

AF:

0.0199

Gnomad OTH exome

AF:

0.0218

GnomAD4 exome

AF:

0.0192

AC:

28030

AN:

1460364

Hom.:

303

Cov.:

AF XY:

0.0195

AC XY:

14157

AN XY:

726258

show subpopulations

Gnomad4 AFR exome

AF:

0.00296

Gnomad4 AMR exome

AF:

0.0137

Gnomad4 ASJ exome

AF:

0.00946

Gnomad4 EAS exome

AF:

0.00287

Gnomad4 SAS exome

AF:

0.0252

Gnomad4 FIN exome

AF:

0.0243

Gnomad4 NFE exome

AF:

0.0201

Gnomad4 OTH exome

AF:

0.0176

GnomAD4 genome

AF:

0.0143

AC:

2181

AN:

152360

Hom.:

Cov.:

AF XY:

0.0150

AC XY:

1115

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.00341

Gnomad4 AMR

AF:

0.0159

Gnomad4 ASJ

AF:

0.00806

Gnomad4 EAS

AF:

0.00443

Gnomad4 SAS

AF:

0.0207

Gnomad4 FIN

AF:

0.0249

Gnomad4 NFE

AF:

0.0191

Gnomad4 OTH

AF:

0.0246

Alfa

AF:

0.0159

Hom.:

Bravo

AF:

0.0132

Asia WGS

AF:

0.0130

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

May 05, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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