rs112583209

Variant names:

• chr8-42374826-C-G
• rs112583209
• NM_014420.3:c.350G>C

Your query was ambiguous. Multiple possible variants found:

• chr8-42374826-C-G
• chr8-42374826-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014420.3(DKK4):​c.350G>C​(p.Gly117Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DKK4 NM_014420.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.230

Genes affected

DKK4 (HGNC:2894): (dickkopf WNT signaling pathway inhibitor 4) 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. Activity of this protein is modulated by binding to the Wnt co-receptor and the co-factor kremen 2. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.053396434).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DKK4	NM_014420.3	c.350G>C	p.Gly117Ala	missense_variant	Exon 3 of 4	ENST00000220812.3	NP_055235.1
DKK4	XM_011544488.3	c.350G>C	p.Gly117Ala	missense_variant	Exon 4 of 5		XP_011542790.1
DKK4	XM_017013316.2	c.350G>C	p.Gly117Ala	missense_variant	Exon 4 of 5		XP_016868805.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DKK4	ENST00000220812.3	c.350G>C	p.Gly117Ala	missense_variant	Exon 3 of 4	1	NM_014420.3	ENSP00000220812.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251480 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135914

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.33
DANN	Benign	0.42
DEOGEN2	Benign	0.16	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0053	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.23	N
REVEL	Benign	0.010
Sift	Benign	0.17	T
Sift4G	Benign	0.41	T
Polyphen		0.020	B
Vest4		0.073
MutPred		0.17		Gain of phosphorylation at T116 (P = 0.2302);
MVP		0.17
MPC		0.15
ClinPred		0.065	T
GERP RS		1.4
Varity_R		0.027
gMVP		0.42

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

Other links and lift over

dbSNP: rs112583209; hg19: chr8-42232344;