rs566255762

chr22-31906501-C-CAGGCTGCACCAGGGTTAGA

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.*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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.30

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]

ACMG classification

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. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DEPDC5	NM_001242896.3	c.*14_*15insAGGGTTAGAAGGCTGCACC		3_prime_UTR_variant	43/43	ENST00000651528.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DEPDC5	ENST00000651528.2	c.*14_*15insAGGGTTAGAAGGCTGCACC		3_prime_UTR_variant	43/43		NM_001242896.3	P4

Frequencies

GnomAD3 genomes AF: 0.0143 AC: 2177 AN: 152242 Hom.: 19 Cov.: 32

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.: 38 AF XY: 0.0184 AC XY: 2483 AN XY: 134868

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.: 32 AF XY: 0.0195 AC XY: 14157 AN XY: 726258

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.: 19 Cov.: 32 AF XY: 0.0150 AC XY: 1115 AN XY: 74512

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.: 5

Bravo AF: 0.0132

Asia WGS AF: 0.0130 AC: 46 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 05, 2020

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs566255762; hg19: chr22-32302487;