11-8776185-C-CACACA

Position:

• chr11-8776185-C-CACACA

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_213618.2(DENND2B):​c.-25-25461_-25-25460insTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00332 in 451,744 control chromosomes in the GnomAD database, including 9 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0043 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (3 hom.)
• Consequence: DENND2B NM_213618.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.449

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 -6 ACMG points.

• BP6: Variant 11-8776185-C-CACACA is Benign according to our data. Variant chr11-8776185-C-CACACA is described in ClinVar as [Likely_benign]. Clinvar id is 2641584.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DENND2B	NM_213618.2	c.-25-25461_-25-25460insTGTGT		intron_variant		ENST00000313726.11	NP_998783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DENND2B	ENST00000313726.11	c.-25-25461_-25-25460insTGTGT		intron_variant		1	NM_213618.2	ENSP00000319678.6

Frequencies

GnomAD3 genomes AF: 0.00432 AC: 652 AN: 150786 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00129

Gnomad AMI AF: 0.00442

Gnomad AMR AF: 0.00198

Gnomad ASJ AF: 0.0133

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00126

Gnomad FIN AF: 0.000952

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00731

Gnomad OTH AF: 0.00485

GnomAD3 exomes AF: 0.00179 AC: 227 AN: 126910 Hom.: 3 AF XY: 0.00160 AC XY: 111 AN XY: 69500

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000743

Gnomad ASJ exome AF: 0.00900

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000226

Gnomad FIN exome AF: 0.000375

Gnomad NFE exome AF: 0.00276

Gnomad OTH exome AF: 0.000505

GnomAD4 exome AF: 0.00283 AC: 852 AN: 300842 Hom.: 3 Cov.: 0 AF XY: 0.00258 AC XY: 442 AN XY: 171262

Gnomad4 AFR exome AF: 0.000817

Gnomad4 AMR exome AF: 0.000884

Gnomad4 ASJ exome AF: 0.0125

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000474

Gnomad4 FIN exome AF: 0.000892

Gnomad4 NFE exome AF: 0.00389

Gnomad4 OTH exome AF: 0.00262

GnomAD4 genome AF: 0.00431 AC: 650 AN: 150902 Hom.: 6 Cov.: 32 AF XY: 0.00409 AC XY: 302 AN XY: 73764

Gnomad4 AFR AF: 0.00128

Gnomad4 AMR AF: 0.00184

Gnomad4 ASJ AF: 0.0133

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00147

Gnomad4 FIN AF: 0.000952

Gnomad4 NFE AF: 0.00730

Gnomad4 OTH AF: 0.00480

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

DENND2B: 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: rs772460904; hg19: chr11-8797732;