4-106984351-G-A

Variant names:

• chr4-106984351-G-A
• rs2866908
• NM_014421.3:c.222+51019C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014421.3(DKK2):​c.222+51019C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 151,834 control chromosomes in the GnomAD database, including 2,928 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 0.19 (2928 hom., cov: 32)
• Consequence: DKK2 NM_014421.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 6 publications found

Genes affected

DKK2 (HGNC:2892): (dickkopf WNT signaling pathway inhibitor 2) 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. It can act as either an agonist or antagonist of Wnt/beta-catenin signaling, depending on the cellular context and the presence of the co-factor kremen 2. Activity of this protein is also modulated by binding to the Wnt co-receptor LDL-receptor related protein 6 (LRP6). [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DKK2	NM_014421.3	c.222+51019C>T		intron_variant	Intron 1 of 3	ENST00000285311.8	NP_055236.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DKK2	ENST00000285311.8	c.222+51019C>T		intron_variant	Intron 1 of 3	1	NM_014421.3	ENSP00000285311.3
DKK2	ENST00000513208.5	c.-78-58402C>T		intron_variant	Intron 2 of 4	1		ENSP00000421255.1
DKK2	ENST00000510534.1	n.443+51019C>T		intron_variant	Intron 1 of 2	1
DKK2	ENST00000510463.1	c.85-58402C>T		intron_variant	Intron 3 of 5	3		ENSP00000423797.1

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28068 AN: 151716 Hom.: 2925 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.185 AC: 28105 AN: 151834 Hom.: 2928 Cov.: 32 AF XY: 0.189 AC XY: 14028 AN XY: 74198

African (AFR) AF: 0.148 AC: 6139 AN: 41396

American (AMR) AF: 0.287 AC: 4368 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 585 AN: 3466

East Asian (EAS) AF: 0.424 AC: 2182 AN: 5148

South Asian (SAS) AF: 0.257 AC: 1236 AN: 4816

European-Finnish (FIN) AF: 0.178 AC: 1874 AN: 10506

Middle Eastern (MID) AF: 0.171 AC: 50 AN: 292

European-Non Finnish (NFE) AF: 0.164 AC: 11146 AN: 67948

Other (OTH) AF: 0.177 AC: 374 AN: 2110

Alfa AF: 0.163 Hom.: 2760

Bravo AF: 0.195

Asia WGS AF: 0.309 AC: 1078 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.069
DANN	Benign	0.75
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2866908; hg19: chr4-107905508;