rs150103661

Variant names:

• chr22-31806103-CTGTT-C
• rs150103661
• NM_001242896.3:c.1218-13_1218-10delGTTT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_001242896.3(DEPDC5):​c.1218-13_1218-10delGTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00117 in 1,602,800 control chromosomes in the GnomAD database, including 17 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0060 (7 hom., cov: 32)
  • Exomes 𝑓: 0.00067 (10 hom.)
• Consequence: DEPDC5 NM_001242896.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3 O:1
• Conservation: PhyloP100: 1.59

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]

ENSG00000285404 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 22-31806103-CTGTT-C is Benign according to our data. Variant chr22-31806103-CTGTT-C is described in ClinVar as [Benign]. Clinvar id is 264754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31806103-CTGTT-C is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00598 (910/152294) while in subpopulation AFR AF= 0.02 (830/41566). AF 95% confidence interval is 0.0188. There are 7 homozygotes in gnomad4. There are 413 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEPDC5	NM_001242896.3	c.1218-13_1218-10delGTTT		intron_variant	Intron 17 of 42	ENST00000651528.2	NP_001229825.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEPDC5	ENST00000651528.2	c.1218-18_1218-15delTGTT		intron_variant	Intron 17 of 42		NM_001242896.3	ENSP00000498382.1
ENSG00000285404	ENST00000646701.1	c.1134-18_1134-15delTGTT		intron_variant	Intron 15 of 20			ENSP00000496158.1

Frequencies

GnomAD3 genomes AF: 0.00591 AC: 900 AN: 152176 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0198

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00347

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00525

GnomAD3 exomes AF: 0.00163 AC: 402 AN: 246514 Hom.: 2 AF XY: 0.00129 AC XY: 173 AN XY: 133970

Gnomad AFR exome AF: 0.0207

Gnomad AMR exome AF: 0.00162

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000205

Gnomad OTH exome AF: 0.000835

GnomAD4 exome AF: 0.000670 AC: 972 AN: 1450506 Hom.: 10 AF XY: 0.000598 AC XY: 432 AN XY: 722422

Gnomad4 AFR exome AF: 0.0197

Gnomad4 AMR exome AF: 0.00213

Gnomad4 ASJ exome AF: 0.0000385

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000350

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000102

Gnomad4 OTH exome AF: 0.00177

GnomAD4 genome AF: 0.00598 AC: 910 AN: 152294 Hom.: 7 Cov.: 32 AF XY: 0.00555 AC XY: 413 AN XY: 74450

Gnomad4 AFR AF: 0.0200

Gnomad4 AMR AF: 0.00347

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.00381 Hom.: 0

Bravo AF: 0.00686

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Aug 08, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 30093711) -

Oct 23, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Familial focal epilepsy with variable foci Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Epilepsy, familial focal, with variable foci 1 Other:1

-

GeneReviews

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs150103661; hg19: chr22-32202089;