11-8852528-T-C

Variant names:

• chr11-8852528-T-C
• rs4910068
• ENST00000534127.5:c.-155-13178A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005418.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DENND2B	NM_001376495.1		c.-288-13178A>G		intron	N/A	NP_001363424.1
	DENND2B	NM_001376496.1		c.-115+18426A>G		intron	N/A	NP_001363425.1
	DENND2B	NM_001376497.1		c.-115+18307A>G		intron	N/A	NP_001363426.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DENND2B	ENST00000534127.5	TSL:1	c.-155-13178A>G		intron	N/A	ENSP00000433528.1
	DENND2B	ENST00000857949.1		c.-114-41193A>G		intron	N/A	ENSP00000528008.1
	DENND2B	ENST00000857950.1		c.-66-13178A>G		intron	N/A	ENSP00000528009.1

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

African (AFR) AF: 0.115 AC: 4739 AN: 41160

American (AMR) AF: 0.240 AC: 3650 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 1305 AN: 3468

East Asian (EAS) AF: 0.0395 AC: 203 AN: 5138

South Asian (SAS) AF: 0.208 AC: 996 AN: 4782

European-Finnish (FIN) AF: 0.237 AC: 2483 AN: 10476

Middle Eastern (MID) AF: 0.372 AC: 107 AN: 288

European-Non Finnish (NFE) AF: 0.261 AC: 17695 AN: 67788

Other (OTH) AF: 0.250 AC: 528 AN: 2110

Alfa AF: 0.253 Hom.: 10180

Bravo AF: 0.207

Asia WGS AF: 0.109 AC: 380 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.4
DANN	Benign	0.84
PhyloP100		0.16
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: rs4910068; hg19: chr11-8874075;