11-8776186-A-ACACACACACACACACC

Variant names:

• chr11-8776186-A-ACACACACACACACACC
• rs761084725
• NM_213618.2:c.-25-25462_-25-25461insGGTGTGTGTGTGTGTG

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_-25-25461insGGTGTGTGTGTGTGTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00198 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 0.0020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00069 (0 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-ACACACACACACACACC is Benign according to our data. Variant chr11-8776186-A-ACACACACACACACACC is described in ClinVar as Benign. ClinVar VariationId is 2641586.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_-25-25461insGGTGTGTGTGTGTGTG		intron	N/A	NP_998783.1	P78524-1
	DENND2B	NM_001376495.1		c.-25-25462_-25-25461insGGTGTGTGTGTGTGTG		intron	N/A	NP_001363424.1	P78524-1
	DENND2B	NM_001376496.1		c.-25-25462_-25-25461insGGTGTGTGTGTGTGTG		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_-25-25461insGGTGTGTGTGTGTGTG		intron	N/A	ENSP00000319678.6	P78524-1
	DENND2B	ENST00000534127.5	TSL:1	c.-25-25462_-25-25461insGGTGTGTGTGTGTGTG		intron	N/A	ENSP00000433528.1	P78524-1
	DENND2B	ENST00000526757.5	TSL:1	c.-25-25462_-25-25461insGGTGTGTGTGTGTGTG		intron	N/A	ENSP00000435097.1	P78524-2

Frequencies

GnomAD3 genomes AF: 0.00199 AC: 285 AN: 143316 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000896

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00247

Gnomad ASJ AF: 0.000309

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000226

Gnomad FIN AF: 0.000101

Gnomad MID AF: 0.00347

Gnomad NFE AF: 0.00327

Gnomad OTH AF: 0.000515

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000686 AC: 205 AN: 298788 Hom.: 0 Cov.: 0 AF XY: 0.000759 AC XY: 129 AN XY: 169962

⚠️ 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: 8516

American (AMR) AF: 0.000409 AC: 11 AN: 26888

Ashkenazi Jewish (ASJ) AF: 0.00124 AC: 13 AN: 10468

East Asian (EAS) AF: 0.00 AC: 0 AN: 9212

South Asian (SAS) AF: 0.000120 AC: 7 AN: 58440

European-Finnish (FIN) AF: 0.0000813 AC: 1 AN: 12306

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2572

European-Non Finnish (NFE) AF: 0.00100 AC: 157 AN: 156358

Other (OTH) AF: 0.000998 AC: 14 AN: 14028

⚠️ 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: 0.00198 AC: 284 AN: 143434 Hom.: 0 Cov.: 32 AF XY: 0.00171 AC XY: 120 AN XY: 70058

African (AFR) AF: 0.000893 AC: 35 AN: 39188

American (AMR) AF: 0.00240 AC: 35 AN: 14596

Ashkenazi Jewish (ASJ) AF: 0.000309 AC: 1 AN: 3232

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

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

European-Finnish (FIN) AF: 0.000101 AC: 1 AN: 9898

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

European-Non Finnish (NFE) AF: 0.00327 AC: 209 AN: 63980

Other (OTH) AF: 0.000509 AC: 1 AN: 1964

Alfa AF: 0.00145 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;