11-8766621-A-T

Variant names:

• chr11-8766621-A-T
• rs10743089
• NM_213618.2:c.-25-15896T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_213618.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DENND2B	NM_213618.2	MANE Select	c.-25-15896T>A		intron	N/A	NP_998783.1	P78524-1
	DENND2B	NM_001376495.1		c.-25-15896T>A		intron	N/A	NP_001363424.1	P78524-1
	DENND2B	NM_001376496.1		c.-25-15896T>A		intron	N/A	NP_001363425.1	P78524-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DENND2B	ENST00000313726.11	TSL:1 MANE Select	c.-25-15896T>A		intron	N/A	ENSP00000319678.6	P78524-1
	DENND2B	ENST00000534127.5	TSL:1	c.-25-15896T>A		intron	N/A	ENSP00000433528.1	P78524-1
	DENND2B	ENST00000526757.5	TSL:1	c.-25-15896T>A		intron	N/A	ENSP00000435097.1	P78524-2

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

GnomAD2 exomes AF: 0.617 AC: 79070 AN: 128190 AF XY: 0.615

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 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

African (AFR) AF: 0.397 AC: 9679 AN: 24398

American (AMR) AF: 0.607 AC: 17134 AN: 28246

Ashkenazi Jewish (ASJ) AF: 0.513 AC: 8175 AN: 15930

East Asian (EAS) AF: 0.649 AC: 8326 AN: 12836

South Asian (SAS) AF: 0.620 AC: 47231 AN: 76138

European-Finnish (FIN) AF: 0.694 AC: 8769 AN: 12638

Middle Eastern (MID) AF: 0.500 AC: 2098 AN: 4192

European-Non Finnish (NFE) AF: 0.669 AC: 615321 AN: 920124

Other (OTH) AF: 0.631 AC: 26171 AN: 41496

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

African (AFR) AF: 0.413 AC: 17143 AN: 41476

American (AMR) AF: 0.582 AC: 8899 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1751 AN: 3468

East Asian (EAS) AF: 0.654 AC: 3378 AN: 5166

South Asian (SAS) AF: 0.623 AC: 3005 AN: 4820

European-Finnish (FIN) AF: 0.697 AC: 7375 AN: 10578

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.658 AC: 44748 AN: 67972

Other (OTH) AF: 0.551 AC: 1163 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	15
DANN	Benign	0.68
PhyloP100		3.8
PromoterAI		-0.018	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10743089; hg19: chr11-8788168;