11-8766621-A-T

Position:

• chr11-8766621-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_213618.2(DENND2B):​c.-25-15896T>A variant causes a intron change. The variant allele was found at a frequency of 0.645 in 1,288,078 control chromosomes in the GnomAD database, including 271,293 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.58 (26666 hom., cov: 32)
  • Exomes 𝑓: 0.65 (244627 hom.)
• Consequence: DENND2B NM_213618.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.77

Genes affected

DENND2B (HGNC:11350): (DENN domain containing 2B) This gene was identified by its ability to suppress the tumorigenicity of Hela cells in nude mice. The protein encoded by this gene contains a C-terminal region that shares similarity with the Rab 3 family of small GTP binding proteins. This protein preferentially binds to the SH3 domain of c-Abl kinase, and acts as a regulator of MAPK1/ERK2 kinase, which may contribute to its ability to reduce the tumorigenic phenotype in cells. Three alternatively spliced transcript variants of this gene encoding distinct isoforms are identified. [provided by RefSeq, Jul 2008]

DENND2B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DENND2B	NM_213618.2	c.-25-15896T>A		intron_variant		ENST00000313726.11	NP_998783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DENND2B	ENST00000313726.11	c.-25-15896T>A		intron_variant		1	NM_213618.2	ENSP00000319678.6

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88260 AN: 151962 Hom.: 26644 Cov.: 32

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.791

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.654

Gnomad SAS AF: 0.623

Gnomad FIN AF: 0.697

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.544

GnomAD3 exomes AF: 0.617 AC: 79070 AN: 128190 Hom.: 24752 AF XY: 0.615 AC XY: 43159 AN XY: 70204

Gnomad AFR exome AF: 0.402

Gnomad AMR exome AF: 0.608

Gnomad ASJ exome AF: 0.511

Gnomad EAS exome AF: 0.657

Gnomad SAS exome AF: 0.618

Gnomad FIN exome AF: 0.692

Gnomad NFE exome AF: 0.648

Gnomad OTH exome AF: 0.622

GnomAD4 exome AF: 0.654 AC: 742904 AN: 1135998 Hom.: 244627 Cov.: 40 AF XY: 0.651 AC XY: 362935 AN XY: 557264

Gnomad4 AFR exome AF: 0.397

Gnomad4 AMR exome AF: 0.607

Gnomad4 ASJ exome AF: 0.513

Gnomad4 EAS exome AF: 0.649

Gnomad4 SAS exome AF: 0.620

Gnomad4 FIN exome AF: 0.694

Gnomad4 NFE exome AF: 0.669

Gnomad4 OTH exome AF: 0.631

GnomAD4 genome AF: 0.581 AC: 88321 AN: 152080 Hom.: 26666 Cov.: 32 AF XY: 0.580 AC XY: 43106 AN XY: 74332

Gnomad4 AFR AF: 0.413

Gnomad4 AMR AF: 0.582

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.654

Gnomad4 SAS AF: 0.623

Gnomad4 FIN AF: 0.697

Gnomad4 NFE AF: 0.658

Gnomad4 OTH AF: 0.551

Alfa AF: 0.597 Hom.: 4977

Bravo AF: 0.567

Asia WGS AF: 0.701 AC: 2436 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	15
DANN	Benign	0.68

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

Other links and lift over

dbSNP: rs10743089; hg19: chr11-8788168;