11-8702644-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_213618.2(DENND2B):c.2648T>C(p.Val883Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00597 in 1,613,966 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V883M) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0048 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0061 ( 42 hom. )

Consequence

DENND2B
NM_213618.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.57

Variant links:

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 links:

RPL27A (HGNC:10329): (ribosomal protein L27a) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L15P family of ribosomal proteins. It is located in the cytoplasm. Variable expression of this gene in colorectal cancers compared to adjacent normal tissues has been observed, although no correlation between the level of expression and the severity of the disease has been found. As is typical for genes encoding ribosomal proteins, multiple processed pseudogenes derived from this gene are dispersed through the genome. [provided by RefSeq, Jul 2008]

RPL27A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01018852).

BP6

Variant 11-8702644-A-G is Benign according to our data. Variant chr11-8702644-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2641582.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DENND2B	NM_213618.2 link	c.2648T>C	p.Val883Ala	missense_variant	Exon 14 of 20	ENST00000313726.11	NP_998783.1	P78524-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DENND2B	ENST00000313726.11 link	c.2648T>C	p.Val883Ala	missense_variant	Exon 14 of 20	1	NM_213618.2	ENSP00000319678.6		P78524-1

Frequencies

GnomAD3 genomes

AF:

0.00476

AC:

724

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.0216

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00607

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00559

AC:

1403

AN:

251170

AF XY:

0.00547

show subpopulations

Gnomad AFR exome

AF:

0.00129

Gnomad AMR exome

AF:

0.00124

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0202

Gnomad NFE exome

AF:

0.00757

Gnomad OTH exome

AF:

0.00424

GnomAD4 exome

AF:

0.00610

AC:

8915

AN:

1461674

Hom.:

Cov.:

AF XY:

0.00587

AC XY:

4271

AN XY:

727136

show subpopulations

Gnomad4 AFR exome

AF:

0.000836

AC:

AN:

33480

Gnomad4 AMR exome

AF:

0.00119

AC:

AN:

44724

Gnomad4 ASJ exome

AF:

0.000115

AC:

AN:

26134

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39700

Gnomad4 SAS exome

AF:

0.000719

AC:

AN:

86258

Gnomad4 FIN exome

AF:

0.0231

AC:

1231

AN:

53212

Gnomad4 NFE exome

AF:

0.00655

AC:

7286

AN:

1112004

Gnomad4 Remaining exome

AF:

0.00414

AC:

250

AN:

60394

Heterozygous variant carriers

543

1087

1630

2174

2717

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

270

540

810

1080

1350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00475

AC:

724

AN:

152292

Hom.:

Cov.:

AF XY:

0.00525

AC XY:

391

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00144

AC:

0.00144286

AN:

0.00144286

Gnomad4 AMR

AF:

0.000850

AC:

0.000849784

AN:

0.000849784

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.000830

AC:

0.000829876

AN:

0.000829876

Gnomad4 FIN

AF:

0.0216

AC:

0.021555

AN:

0.021555

Gnomad4 NFE

AF:

0.00607

AC:

0.00607228

AN:

0.00607228

Gnomad4 OTH

AF:

0.00237

AC:

0.00236518

AN:

0.00236518

Heterozygous variant carriers

121

161

201

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00593

Hom.:

Bravo

AF:

0.00338

TwinsUK

AF:

0.00539

AC:

ALSPAC

AF:

0.00467

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.00559

AC:

ExAC

AF:

0.00610

AC:

741

EpiCase

AF:

0.00622

EpiControl

AF:

0.00569

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

DENND2B: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

.;T;T;.;T;T;.

Eigen

Uncertain

0.21

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.81

.;.;T;T;T;T;T

MetaRNN

Benign

0.010

T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

.;M;M;.;.;.;.

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-3.6

D;D;D;D;D;D;D

REVEL

Uncertain

0.38

Sift

Benign

0.10

T;D;D;T;T;T;T

Sift4G

Benign

0.091

T;D;D;T;T;T;T

Polyphen

0.012

B;B;B;.;B;.;B

Vest4

0.57

MVP

0.51

MPC

1.5

ClinPred

0.045

GERP RS

4.7

Varity_R

0.42

gMVP

0.71

Mutation Taster

=97/3

polymorphism

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over