11-8732182-A-G

Position:

• chr11-8732182-A-G

Variant summary

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

The NM_213618.2(DENND2B):​c.81-973T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 152,182 control chromosomes in the GnomAD database, including 10,946 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 0.34 (10946 hom., cov: 33)
• Consequence: DENND2B NM_213618.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0310

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DENND2B	NM_213618.2	c.81-973T>C		intron_variant		ENST00000313726.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DENND2B	ENST00000313726.11	c.81-973T>C		intron_variant		1	NM_213618.2	A1

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52178 AN: 152064 Hom.: 10937 Cov.: 33

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.322

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.343 AC: 52195 AN: 152182 Hom.: 10946 Cov.: 33 AF XY: 0.346 AC XY: 25768 AN XY: 74380

Gnomad4 AFR AF: 0.100

Gnomad4 AMR AF: 0.411

Gnomad4 ASJ AF: 0.317

Gnomad4 EAS AF: 0.361

Gnomad4 SAS AF: 0.283

Gnomad4 FIN AF: 0.551

Gnomad4 NFE AF: 0.446

Gnomad4 OTH AF: 0.319

Alfa AF: 0.414 Hom.: 17964

Bravo AF: 0.325

Asia WGS AF: 0.282 AC: 980 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.6
DANN	Benign	0.46

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: rs905290; hg19: chr11-8753729;