NM_014421.3:c.223-26727T>C

Variant names:

• chr4-106952676-A-G
• rs411143
• NM_014421.3:c.223-26727T>C

Variant summary

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

The NM_014421.3(DKK2):​c.223-26727T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 152,022 control chromosomes in the GnomAD database, including 6,795 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 0.29 (6795 hom., cov: 32)
• Consequence: DKK2 NM_014421.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110
• Publications: 1 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DKK2	NM_014421.3	c.223-26727T>C		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.223-26727T>C		intron_variant	Intron 1 of 3	1	NM_014421.3	ENSP00000285311.3
DKK2	ENST00000513208.5	c.-78-26727T>C		intron_variant	Intron 2 of 4	1		ENSP00000421255.1
DKK2	ENST00000510534.1	n.444-26727T>C		intron_variant	Intron 1 of 2	1
DKK2	ENST00000510463.1	c.85-26727T>C		intron_variant	Intron 3 of 5	3		ENSP00000423797.1

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44528 AN: 151904 Hom.: 6788 Cov.: 32

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.293 AC: 44579 AN: 152022 Hom.: 6795 Cov.: 32 AF XY: 0.292 AC XY: 21713 AN XY: 74290

African (AFR) AF: 0.379 AC: 15716 AN: 41468

American (AMR) AF: 0.201 AC: 3066 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 939 AN: 3470

East Asian (EAS) AF: 0.299 AC: 1547 AN: 5178

South Asian (SAS) AF: 0.212 AC: 1023 AN: 4830

European-Finnish (FIN) AF: 0.331 AC: 3497 AN: 10564

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.264 AC: 17906 AN: 67938

Other (OTH) AF: 0.274 AC: 577 AN: 2106

Alfa AF: 0.279 Hom.: 1017

Bravo AF: 0.284

Asia WGS AF: 0.247 AC: 857 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.9
DANN	Benign	0.87
PhyloP100		0.011
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: rs411143; hg19: chr4-107873833;