Variant 10-52316550-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_012242.4(DKK1):c.548-4G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00327 in 1,613,576 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0038 ( 6 hom., cov: 33)

Exomes 𝑓: 0.0032 ( 12 hom. )

Consequence

DKK1
NM_012242.4 splice_region, intron

Scores

Splicing: ADA: 0.00001591

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.16

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 10-52316550-G-A is Benign according to our data. Variant chr10-52316550-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 773234.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 571 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DKK1	NM_012242.4 link	c.548-4G>A		splice_region_variant, intron_variant	Intron 3 of 3	ENST00000373970.4	NP_036374.1	O94907I1W660

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
DKK1	ENST00000373970.4 link	c.548-4G>A	splice_region_variant, intron_variant	Intron 3 of 3	1	NM_012242.4	ENSP00000363081.3	O94907
DKK1	ENST00000476752.1 link	n.197-4G>A	splice_region_variant, intron_variant	Intron 2 of 2	2
DKK1	ENST00000494277.5 link	n.171-4G>A	splice_region_variant, intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes

AF:

0.00375

AC:

571

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000580

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0145

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00550

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00355

AC:

890

AN:

250922

Hom.:

AF XY:

0.00358

AC XY:

485

AN XY:

135590

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.000377

Gnomad ASJ exome

AF:

0.00258

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0136

Gnomad NFE exome

AF:

0.00467

Gnomad OTH exome

AF:

0.00262

GnomAD4 exome

AF:

0.00322

AC:

4704

AN:

1461380

Hom.:

Cov.:

AF XY:

0.00329

AC XY:

2389

AN XY:

726946

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.000582

Gnomad4 ASJ exome

AF:

0.00280

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.0141

Gnomad4 NFE exome

AF:

0.00329

Gnomad4 OTH exome

AF:

0.00295

GnomAD4 genome

AF:

0.00375

AC:

571

AN:

152196

Hom.:

Cov.:

AF XY:

0.00388

AC XY:

289

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.000578

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0145

Gnomad4 NFE

AF:

0.00550

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00428

Hom.:

Bravo

AF:

0.00206

EpiCase

AF:

0.00311

EpiControl

AF:

0.00290

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

DKK1: BP4, BS2 -

Jul 26, 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

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.4

DANN

Benign

0.70

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000016

dbscSNV1_RF

Benign

0.012

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