chr22-31806103-CTGTT-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• epilepsy, familial focal, with variable foci 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Ambry Genetics, Illumina, G2P
• focal epilepsy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• autosomal dominant epilepsy with auditory features

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal dominant nocturnal frontal lobe epilepsy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• familial focal epilepsy with variable foci

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Brugada syndrome

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000285404 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 264754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 910 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001242896.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEPDC5	NM_001242896.3	MANE Select	c.1218-13_1218-10delGTTT		intron	N/A	NP_001229825.1
	DEPDC5	NM_001364318.2		c.1218-13_1218-10delGTTT		intron	N/A	NP_001351247.1
	DEPDC5	NM_001136029.4		c.1218-13_1218-10delGTTT		intron	N/A	NP_001129501.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEPDC5	ENST00000651528.2	MANE Select	c.1218-18_1218-15delTGTT		intron	N/A	ENSP00000498382.1
	DEPDC5	ENST00000382112.8	TSL:1	c.1218-18_1218-15delTGTT		intron	N/A	ENSP00000371546.4
	DEPDC5	ENST00000433147.2	TSL:1	c.1134-18_1134-15delTGTT		intron	N/A	ENSP00000410544.2

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

GnomAD2 exomes AF: 0.00163 AC: 402 AN: 246514 AF XY: 0.00129

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 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

African (AFR) AF: 0.0197 AC: 648 AN: 32936

American (AMR) AF: 0.00213 AC: 93 AN: 43560

Ashkenazi Jewish (ASJ) AF: 0.0000385 AC: 1 AN: 25958

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39628

South Asian (SAS) AF: 0.0000350 AC: 3 AN: 85644

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53352

Middle Eastern (MID) AF: 0.00122 AC: 7 AN: 5718

European-Non Finnish (NFE) AF: 0.000102 AC: 113 AN: 1103752

Other (OTH) AF: 0.00177 AC: 106 AN: 59958

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

African (AFR) AF: 0.0200 AC: 830 AN: 41566

American (AMR) AF: 0.00347 AC: 53 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68030

Other (OTH) AF: 0.00520 AC: 11 AN: 2116

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

Oct 23, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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)

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 v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs150103661; hg19: chr22-32202089;