11-8776185-C-CACACA

Variant names:

• chr11-8776185-C-CACACA
• rs772460904
• NM_213618.2:c.-25-25461_-25-25460insTGTGT

Variant summary

Our verdict is Likely benign. The variant received -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
• 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 -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 VariationId is 2641584.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 6 gene

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.-25-25461_-25-25460insTGTGT		intron	N/A	NP_998783.1	P78524-1
	DENND2B	NM_001376495.1		c.-25-25461_-25-25460insTGTGT		intron	N/A	NP_001363424.1	P78524-1
	DENND2B	NM_001376496.1		c.-25-25461_-25-25460insTGTGT		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.-25-25461_-25-25460insTGTGT		intron	N/A	ENSP00000319678.6	P78524-1
	DENND2B	ENST00000534127.5	TSL:1	c.-25-25461_-25-25460insTGTGT		intron	N/A	ENSP00000433528.1	P78524-1
	DENND2B	ENST00000526757.5	TSL:1	c.-25-25461_-25-25460insTGTGT		intron	N/A	ENSP00000435097.1	P78524-2

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

GnomAD2 exomes AF: 0.00179 AC: 227 AN: 126910 AF XY: 0.00160

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 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

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

African (AFR) AF: 0.000817 AC: 7 AN: 8572

American (AMR) AF: 0.000884 AC: 24 AN: 27138

Ashkenazi Jewish (ASJ) AF: 0.0125 AC: 134 AN: 10684

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

South Asian (SAS) AF: 0.000474 AC: 28 AN: 59042

European-Finnish (FIN) AF: 0.000892 AC: 11 AN: 12328

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2718

European-Non Finnish (NFE) AF: 0.00389 AC: 611 AN: 157020

Other (OTH) AF: 0.00262 AC: 37 AN: 14128

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

African (AFR) AF: 0.00128 AC: 53 AN: 41284

American (AMR) AF: 0.00184 AC: 28 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.0133 AC: 46 AN: 3460

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5144

South Asian (SAS) AF: 0.00147 AC: 7 AN: 4746

European-Finnish (FIN) AF: 0.000952 AC: 10 AN: 10502

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00730 AC: 491 AN: 67276

Other (OTH) AF: 0.00480 AC: 10 AN: 2084

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely 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		-0.45
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: rs772460904; hg19: chr11-8797732;