11-8766621-A-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_213618.2(DENND2B):​c.-25-15896T>G variant causes a intron change. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000018 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).

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

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

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000780 AC: 1 AN: 128190 AF XY: 0.0000142

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000176 AC: 2 AN: 1136730 Hom.: 0 Cov.: 40 AF XY: 0.00000359 AC XY: 2 AN XY: 557616

African (AFR) AF: 0.00 AC: 0 AN: 24408

American (AMR) AF: 0.00 AC: 0 AN: 28258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15938

East Asian (EAS) AF: 0.00 AC: 0 AN: 12840

South Asian (SAS) AF: 0.0000263 AC: 2 AN: 76184

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12642

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4202

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 920744

Other (OTH) AF: 0.00 AC: 0 AN: 41514

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	14
DANN	Benign	0.57
PhyloP100		3.8
PromoterAI		0.011	Neutral

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;