11-8852528-T-C

Position:

• chr11-8852528-T-C

Variant summary

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

The NM_005418.4(DENND2B):​c.-155-13178A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 151,342 control chromosomes in the GnomAD database, including 3,825 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 0.21 (3825 hom., cov: 32)
• Consequence: DENND2B NM_005418.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.163

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DENND2B	NM_001376495.1	c.-288-13178A>G		intron_variant			NP_001363424.1
DENND2B	NM_001376496.1	c.-115+18426A>G		intron_variant			NP_001363425.1
DENND2B	NM_001376497.1	c.-115+18307A>G		intron_variant			NP_001363426.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DENND2B	ENST00000534127.5	c.-155-13178A>G		intron_variant		1		ENSP00000433528.1
DENND2B	ENST00000526241.5	c.-66-13178A>G		intron_variant		3		ENSP00000433346.1
DENND2B	ENST00000526155.5	c.-115+18426A>G		intron_variant		2		ENSP00000431139.1

Frequencies

GnomAD3 genomes AF: 0.211 AC: 31980 AN: 151224 Hom.: 3821 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.0394

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.254

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

GnomAD4 genome AF: 0.211 AC: 31980 AN: 151342 Hom.: 3825 Cov.: 32 AF XY: 0.210 AC XY: 15549 AN XY: 73932

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.240

Gnomad4 ASJ AF: 0.376

Gnomad4 EAS AF: 0.0395

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.237

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.250

Alfa AF: 0.261 Hom.: 7312

Bravo AF: 0.207

Asia WGS AF: 0.109 AC: 380 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.4
DANN	Benign	0.84

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: rs4910068; hg19: chr11-8874075;