11-8708304-T-G

Position:

• chr11-8708304-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_213618.2(DENND2B):​c.2353-450A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0104 in 985,464 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0064 (8 hom., cov: 32)
  • Exomes 𝑓: 0.011 (55 hom.)
• Consequence: DENND2B NM_213618.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.362

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 11-8708304-T-G is Benign according to our data. Variant chr11-8708304-T-G is described in ClinVar as [Benign]. Clinvar id is 2641583.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DENND2B	NM_213618.2	c.2353-450A>C		intron_variant		ENST00000313726.11	NP_998783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DENND2B	ENST00000313726.11	c.2353-450A>C		intron_variant		1	NM_213618.2	ENSP00000319678.6

Frequencies

GnomAD3 genomes AF: 0.00644 AC: 981 AN: 152244 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.00181

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00353

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00320

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0116

Gnomad OTH AF: 0.00573

GnomAD4 exome AF: 0.0111 AC: 9237 AN: 833102 Hom.: 55 Cov.: 29 AF XY: 0.0110 AC XY: 4246 AN XY: 384712

Gnomad4 AFR exome AF: 0.000824

Gnomad4 AMR exome AF: 0.00508

Gnomad4 ASJ exome AF: 0.00252

Gnomad4 EAS exome AF: 0.000551

Gnomad4 SAS exome AF: 0.00237

Gnomad4 FIN exome AF: 0.00362

Gnomad4 NFE exome AF: 0.0118

Gnomad4 OTH exome AF: 0.00729

GnomAD4 genome AF: 0.00645 AC: 982 AN: 152362 Hom.: 8 Cov.: 32 AF XY: 0.00552 AC XY: 411 AN XY: 74504

Gnomad4 AFR AF: 0.00180

Gnomad4 AMR AF: 0.00353

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00320

Gnomad4 NFE AF: 0.0116

Gnomad4 OTH AF: 0.00567

Alfa AF: 0.00719 Hom.: 1

Bravo AF: 0.00625

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2022

DENND2B: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.8
DANN	Benign	0.66

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: rs117295970; hg19: chr11-8729851;