chr11-8776186-A-ACACACACACACACACACACC

Variant names:

• chr11-8776186-A-ACACACACACACACACACACC
• rs761084725
• NM_213618.2:c.-25-25462_-25-25461insGGTGTGTGTGTGTGTGTGTG

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_-25-25461insGGTGTGTGTGTGTGTGTGTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00207 in 143,408 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 0.0021 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00052 (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-ACACACACACACACACACACC is Benign according to our data. Variant chr11-8776186-A-ACACACACACACACACACACC is described in ClinVar as Benign. ClinVar VariationId is 2641585.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_-25-25461insGGTGTGTGTGTGTGTGTGTG		intron	N/A	NP_998783.1	P78524-1
	DENND2B	NM_001376495.1		c.-25-25462_-25-25461insGGTGTGTGTGTGTGTGTGTG		intron	N/A	NP_001363424.1	P78524-1
	DENND2B	NM_001376496.1		c.-25-25462_-25-25461insGGTGTGTGTGTGTGTGTGTG		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_-25-25461insGGTGTGTGTGTGTGTGTGTG		intron	N/A	ENSP00000319678.6	P78524-1
	DENND2B	ENST00000534127.5	TSL:1	c.-25-25462_-25-25461insGGTGTGTGTGTGTGTGTGTG		intron	N/A	ENSP00000433528.1	P78524-1
	DENND2B	ENST00000526757.5	TSL:1	c.-25-25462_-25-25461insGGTGTGTGTGTGTGTGTGTG		intron	N/A	ENSP00000435097.1	P78524-2

Frequencies

GnomAD3 genomes AF: 0.00207 AC: 297 AN: 143290 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000666

Gnomad AMI AF: 0.00228

Gnomad AMR AF: 0.00384

Gnomad ASJ AF: 0.000310

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00113

Gnomad FIN AF: 0.000606

Gnomad MID AF: 0.00347

Gnomad NFE AF: 0.00297

Gnomad OTH AF: 0.00516

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000519 AC: 155 AN: 298800 Hom.: 1 Cov.: 0 AF XY: 0.000471 AC XY: 80 AN XY: 169966

⚠️ 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: 8512

American (AMR) AF: 0.000260 AC: 7 AN: 26882

Ashkenazi Jewish (ASJ) AF: 0.000476 AC: 5 AN: 10508

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

South Asian (SAS) AF: 0.000377 AC: 22 AN: 58336

European-Finnish (FIN) AF: 0.000407 AC: 5 AN: 12290

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

European-Non Finnish (NFE) AF: 0.000658 AC: 103 AN: 156450

Other (OTH) AF: 0.000713 AC: 10 AN: 14032

⚠️ 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: 0.00207 AC: 297 AN: 143408 Hom.: 0 Cov.: 32 AF XY: 0.00193 AC XY: 135 AN XY: 70040

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

African (AFR) AF: 0.000664 AC: 26 AN: 39180

American (AMR) AF: 0.00384 AC: 56 AN: 14592

Ashkenazi Jewish (ASJ) AF: 0.000310 AC: 1 AN: 3230

East Asian (EAS) AF: 0.00 AC: 0 AN: 5012

South Asian (SAS) AF: 0.00113 AC: 5 AN: 4418

European-Finnish (FIN) AF: 0.000606 AC: 6 AN: 9894

Middle Eastern (MID) AF: 0.00376 AC: 1 AN: 266

European-Non Finnish (NFE) AF: 0.00297 AC: 190 AN: 63976

Other (OTH) AF: 0.00510 AC: 10 AN: 1962

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00232 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
Mutation Taster		=100/0	polymorphism

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;