Variant 11-12002374-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001018057.2(DKK3):c.277A>G(p.Ser93Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000499 in 1,614,162 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0029 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00025 ( 3 hom. )

Consequence

DKK3
NM_001018057.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.22

Variant links:

Genes affected

DKK3 (HGNC:2893): (dickkopf WNT signaling pathway inhibitor 3) This gene encodes a protein that is a member of the dickkopf family. The secreted protein contains two cysteine rich regions and is involved in embryonic development through its interactions with the Wnt signaling pathway. The expression of this gene is decreased in a variety of cancer cell lines and it may function as a tumor suppressor gene. Alternative splicing results in multiple transcript variants encoding the same protein. [provided by RefSeq, Jul 2008]

DKK3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007977605).

BP6

Variant 11-12002374-T-C is Benign according to our data. Variant chr11-12002374-T-C is described in ClinVar as [Benign]. Clinvar id is 711543.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DKK3	NM_001018057.2 linkuse as main transcript	c.277A>G	p.Ser93Gly	missense_variant	2/7	ENST00000683431.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DKK3	ENST00000683431.1 linkuse as main transcript	c.277A>G	p.Ser93Gly	missense_variant	2/7		NM_001018057.2	P1

Frequencies

GnomAD3 genomes

AF:

0.00290

AC:

441

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00994

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.000787

AC:

198

AN:

251440

Hom.:

AF XY:

0.000567

AC XY:

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.0109

Gnomad AMR exome

AF:

0.000520

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000248

AC:

363

AN:

1461842

Hom.:

Cov.:

AF XY:

0.000201

AC XY:

146

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.00839

Gnomad4 AMR exome

AF:

0.000738

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000809

Gnomad4 OTH exome

AF:

0.000662

GnomAD4 genome

AF:

0.00291

AC:

443

AN:

152320

Hom.:

Cov.:

AF XY:

0.00286

AC XY:

213

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00996

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000865

Hom.:

Bravo

AF:

0.00326

ESP6500AA

AF:

0.0114

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00101

AC:

122

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.45

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.22

T;T;.;T;.;.

Eigen

Benign

0.062

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.81

MetaRNN

Benign

0.0080

T;T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.9

L;L;.;.;.;.

MutationTaster

Benign

0.95

N;N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.5

N;N;N;N;N;N

REVEL

Benign

0.038

Sift

Uncertain

0.025

D;D;D;D;D;D

Sift4G

Uncertain

0.041

D;D;D;.;.;D

Polyphen

0.15

B;B;B;.;.;.

Vest4

0.27

MVP

0.54

MPC

0.36

ClinPred

0.028

GERP RS

5.5

Varity_R

0.14

gMVP

0.17

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