chr4-107032722-G-T

Variant names:

• chr4-107032722-G-T
• rs956137
• NM_014421.3:c.222+2648C>A

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+2648C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0906 in 152,098 control chromosomes in the GnomAD database, including 690 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 0.091 (690 hom., cov: 33)
• Consequence: DKK2 NM_014421.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.489
• Publications: 3 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DKK2	NM_014421.3	c.222+2648C>A		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+2648C>A		intron_variant	Intron 1 of 3	1	NM_014421.3	ENSP00000285311.3
DKK2	ENST00000513208.5	c.-78-106773C>A		intron_variant	Intron 2 of 4	1		ENSP00000421255.1
DKK2	ENST00000510534.1	n.443+2648C>A		intron_variant	Intron 1 of 2	1
DKK2	ENST00000510463.1	c.84+95220C>A		intron_variant	Intron 3 of 5	3		ENSP00000423797.1

Frequencies

GnomAD3 genomes AF: 0.0906 AC: 13771 AN: 151982 Hom.: 689 Cov.: 33

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.0690

Gnomad ASJ AF: 0.0733

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.0718

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0888

Gnomad OTH AF: 0.103

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

GnomAD4 genome AF: 0.0906 AC: 13778 AN: 152098 Hom.: 690 Cov.: 33 AF XY: 0.0878 AC XY: 6526 AN XY: 74354

African (AFR) AF: 0.117 AC: 4856 AN: 41526

American (AMR) AF: 0.0689 AC: 1053 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0733 AC: 254 AN: 3464

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5184

South Asian (SAS) AF: 0.106 AC: 510 AN: 4824

European-Finnish (FIN) AF: 0.0718 AC: 760 AN: 10586

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0888 AC: 6031 AN: 67914

Other (OTH) AF: 0.101 AC: 213 AN: 2106

Alfa AF: 0.0889 Hom.: 968

Bravo AF: 0.0901

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.24
DANN	Benign	0.25
PhyloP100		-0.49
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: rs956137; hg19: chr4-107953879;