11-8776186-A-ACACACACACACACC

Position:

• chr11-8776186-A-ACACACACACACACC

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_213618.2(DENND2B):​c.-25-25462_-25-25461insGGTGTGTGTGTGTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000844 in 143,434 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00084 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00035 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: DENND2B NM_213618.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.461

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 Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 11-8776186-A-ACACACACACACACC is Benign according to our data. Variant chr11-8776186-A-ACACACACACACACC is described in ClinVar as [Benign]. Clinvar id is 2641587.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DENND2B	NM_213618.2	c.-25-25462_-25-25461insGGTGTGTGTGTGTG		intron_variant		ENST00000313726.11	NP_998783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DENND2B	ENST00000313726.11	c.-25-25462_-25-25461insGGTGTGTGTGTGTG		intron_variant		1	NM_213618.2	ENSP00000319678.6

Frequencies

GnomAD3 genomes AF: 0.000844 AC: 121 AN: 143316 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000179

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000343

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000199

Gnomad SAS AF: 0.000226

Gnomad FIN AF: 0.000505

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00156

Gnomad OTH AF: 0.00103

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000348 AC: 104 AN: 299268 Hom.: 1 Cov.: 0 AF XY: 0.000276 AC XY: 47 AN XY: 170216

Gnomad4 AFR exome AF: 0.000235

Gnomad4 AMR exome AF: 0.000223

Gnomad4 ASJ exome AF: 0.0000952

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000513

Gnomad4 FIN exome AF: 0.000162

Gnomad4 NFE exome AF: 0.000530

Gnomad4 OTH exome AF: 0.000427

GnomAD4 genome AF: 0.000844 AC: 121 AN: 143434 Hom.: 0 Cov.: 32 AF XY: 0.000757 AC XY: 53 AN XY: 70052

Gnomad4 AFR AF: 0.000179

Gnomad4 AMR AF: 0.000343

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000200

Gnomad4 SAS AF: 0.000226

Gnomad4 FIN AF: 0.000505

Gnomad4 NFE AF: 0.00156

Gnomad4 OTH AF: 0.00102

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

Jun 01, 2022

DENND2B: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs761084725; hg19: chr11-8797733;