11-8776186-A-ACACACACACACACACACACCCC

Variant names:

• chr11-8776186-A-ACACACACACACACACACACCCC
• rs761084725
• NM_213618.2:c.-25-25462_-25-25461insGGGGTGTGTGTGTGTGTGTGTG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_213618.2(DENND2B):​c.-25-25462_-25-25461insGGGGTGTGTGTGTGTGTGTGTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000558 in 143,452 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000056 (0 hom., cov: 32)
• Consequence: DENND2B NM_213618.2 intron
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

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_-25-25461insGGGGTGTGTGTGTGTGTGTGTG		intron	N/A	NP_998783.1	P78524-1
	DENND2B	NM_001376495.1		c.-25-25462_-25-25461insGGGGTGTGTGTGTGTGTGTGTG		intron	N/A	NP_001363424.1	P78524-1
	DENND2B	NM_001376496.1		c.-25-25462_-25-25461insGGGGTGTGTGTGTGTGTGTGTG		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_-25-25461insGGGGTGTGTGTGTGTGTGTGTG		intron	N/A	ENSP00000319678.6	P78524-1
	DENND2B	ENST00000534127.5	TSL:1	c.-25-25462_-25-25461insGGGGTGTGTGTGTGTGTGTGTG		intron	N/A	ENSP00000433528.1	P78524-1
	DENND2B	ENST00000526757.5	TSL:1	c.-25-25462_-25-25461insGGGGTGTGTGTGTGTGTGTGTG		intron	N/A	ENSP00000435097.1	P78524-2

Frequencies

GnomAD3 genomes AF: 0.0000558 AC: 8 AN: 143334 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000343

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000199

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000312

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.0000558 AC: 8 AN: 143452 Hom.: 0 Cov.: 32 AF XY: 0.0000571 AC XY: 4 AN XY: 70064

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

African (AFR) AF: 0.00 AC: 0 AN: 39188

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: 0.00 AC: 0 AN: 4418

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9898

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

European-Non Finnish (NFE) AF: 0.0000313 AC: 2 AN: 63996

Other (OTH) AF: 0.00 AC: 0 AN: 1964

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000670321), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 1

ClinVar

Not reported in ClinVar

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;