11-8776186-A-ACACACACACACACC

Variant names:

• chr11-8776186-A-ACACACACACACACC
• rs761084725
• NM_213618.2:c.-25-25462_-25-25461insGGTGTGTGTGTGTG

Variant summary

Our verdict is Likely benign. The variant received -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. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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
• Publications: 0 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]

DENND2B-AS1 (HGNC:56176): (DENND2B antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -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 VariationId is 2641587.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DENND2B	NM_213618.2	MANE Select	c.-25-25462_-25-25461insGGTGTGTGTGTGTG		intron	N/A	NP_998783.1	P78524-1
	DENND2B	NM_001376495.1		c.-25-25462_-25-25461insGGTGTGTGTGTGTG		intron	N/A	NP_001363424.1	P78524-1
	DENND2B	NM_001376496.1		c.-25-25462_-25-25461insGGTGTGTGTGTGTG		intron	N/A	NP_001363425.1	P78524-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DENND2B	ENST00000313726.11	TSL:1 MANE Select	c.-25-25462_-25-25461insGGTGTGTGTGTGTG		intron	N/A	ENSP00000319678.6	P78524-1
	DENND2B	ENST00000534127.5	TSL:1	c.-25-25462_-25-25461insGGTGTGTGTGTGTG		intron	N/A	ENSP00000433528.1	P78524-1
	DENND2B	ENST00000526757.5	TSL:1	c.-25-25462_-25-25461insGGTGTGTGTGTGTG		intron	N/A	ENSP00000435097.1	P78524-2

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000235 AC: 2 AN: 8520

American (AMR) AF: 0.000223 AC: 6 AN: 26908

Ashkenazi Jewish (ASJ) AF: 0.0000952 AC: 1 AN: 10500

East Asian (EAS) AF: 0.00 AC: 0 AN: 9214

South Asian (SAS) AF: 0.0000513 AC: 3 AN: 58454

European-Finnish (FIN) AF: 0.000162 AC: 2 AN: 12310

Middle Eastern (MID) AF: 0.000388 AC: 1 AN: 2576

European-Non Finnish (NFE) AF: 0.000530 AC: 83 AN: 156728

Other (OTH) AF: 0.000427 AC: 6 AN: 14058

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.000179 AC: 7 AN: 39186

American (AMR) AF: 0.000343 AC: 5 AN: 14598

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3232

East Asian (EAS) AF: 0.000200 AC: 1 AN: 5012

South Asian (SAS) AF: 0.000226 AC: 1 AN: 4418

European-Finnish (FIN) AF: 0.000505 AC: 5 AN: 9898

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 266

European-Non Finnish (NFE) AF: 0.00156 AC: 100 AN: 63980

Other (OTH) AF: 0.00102 AC: 2 AN: 1964

Alfa AF: 0.00 Hom.: 1

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.46

Splicing

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

Other links and lift over

dbSNP: rs761084725; hg19: chr11-8797733;