rs16905816

Positions:

• chr11-8777306-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_213618.2(DENND2B):​c.-25-26581C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0789 in 152,248 control chromosomes in the GnomAD database, including 1,447 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.079 (1447 hom., cov: 33)
• Consequence: DENND2B NM_213618.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0320

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DENND2B	NM_213618.2	c.-25-26581C>G		intron_variant		ENST00000313726.11
DENND2B-AS1	NR_120590.1	n.45-6713G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DENND2B	ENST00000313726.11	c.-25-26581C>G		intron_variant		1	NM_213618.2	A1

Frequencies

GnomAD3 genomes AF: 0.0787 AC: 11980 AN: 152130 Hom.: 1442 Cov.: 33

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0238

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.0128

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00107

Gnomad OTH AF: 0.0535

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0789 AC: 12017 AN: 152248 Hom.: 1447 Cov.: 33 AF XY: 0.0773 AC XY: 5758 AN XY: 74458

Gnomad4 AFR AF: 0.259

Gnomad4 AMR AF: 0.0240

Gnomad4 ASJ AF: 0.0115

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.0128

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00107

Gnomad4 OTH AF: 0.0530

Alfa AF: 0.0471 Hom.: 89

Bravo AF: 0.0915

Asia WGS AF: 0.0530 AC: 182 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.4
DANN	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs16905816; hg19: chr11-8798853;