Variant rs140471040 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_012242.4(DKK1):c.46A>C(p.Met16Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000692 in 1,613,810 control chromosomes in the GnomAD database, including 5 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 0.0039 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00036 ( 2 hom. )

Consequence

DKK1
NM_012242.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.11

Variant links:

Genes affected

DKK1 (HGNC:2891): (dickkopf WNT signaling pathway inhibitor 1) This gene encodes a member of the dickkopf family of proteins. Members of this family are secreted proteins characterized by two cysteine-rich domains that mediate protein-protein interactions. The encoded protein binds to the LRP6 co-receptor and inhibits beta-catenin-dependent Wnt signaling. This gene plays a role in embryonic development and may be important in bone formation in adults. Elevated expression of this gene has been observed in numerous human cancers and this protein may promote proliferation, invasion and growth in cancer cell lines. [provided by RefSeq, Sep 2017]

DKK1 links:

PRKG1-AS1 (HGNC:45029): (PRKG1 antisense RNA 1)

PRKG1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003363043).

BP6

Variant 10-52314480-A-C is Benign according to our data. Variant chr10-52314480-A-C is described in ClinVar as [Benign]. Clinvar id is 783572.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 589 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DKK1	NM_012242.4 link	c.46A>C	p.Met16Leu	missense_variant	Exon 1 of 4	ENST00000373970.4	NP_036374.1	O94907I1W660

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DKK1	ENST00000373970.4 link	c.46A>C	p.Met16Leu	missense_variant	Exon 1 of 4	1	NM_012242.4	ENSP00000363081.3		O94907
PRKG1-AS1	ENST00000649494.1 link	n.28T>G		non_coding_transcript_exon_variant	Exon 1 of 8

Frequencies

GnomAD3 genomes

AF:

0.00384

AC:

583

AN:

151960

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0137

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000917

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:

0.0000294

Gnomad OTH

AF:

0.000962

GnomAD3 exomes

AF:

0.000962

AC:

241

AN:

250446

Hom.:

AF XY:

0.000759

AC XY:

103

AN XY:

135708

show subpopulations

Gnomad AFR exome

AF:

0.0141

Gnomad AMR exome

AF:

0.000376

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:

0.00000884

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000361

AC:

527

AN:

1461730

Hom.:

Cov.:

AF XY:

0.000301

AC XY:

219

AN XY:

727174

show subpopulations

Gnomad4 AFR exome

AF:

0.0130

Gnomad4 AMR exome

AF:

0.000380

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00109

GnomAD4 genome

AF:

0.00387

AC:

589

AN:

152080

Hom.:

Cov.:

AF XY:

0.00402

AC XY:

299

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0138

Gnomad4 AMR

AF:

0.000916

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000951

Alfa

AF:

0.000606

Hom.:

Bravo

AF:

0.00447

ESP6500AA

AF:

0.0132

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00125

AC:

152

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 31, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.78

CADD

Benign

5.9

DANN

Benign

0.47

DEOGEN2

Benign

0.35

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0023

LIST_S2

Benign

0.25

MetaRNN

Benign

0.0034

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-1.1

PrimateAI

Uncertain

0.65

PROVEAN

Benign

0.070

REVEL

Benign

0.043

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.17

MutPred

0.35

Loss of MoRF binding (P = 0.0978);

MVP

0.35

MPC

0.41

ClinPred

0.0022

GERP RS

1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.073

gMVP

0.12

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