10-52314480-ATG-CTC

Variant names:

• chr10-52314480-ATG-CTC
• NM_012242.4:c.46_48delATGinsCTC
• DKK1 p.Met16Leu

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_012242.4(DKK1):​c.46_48delATGinsCTC​(p.Met16Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DKK1 NM_012242.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.50
• Publications: 0 publications found

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]

PRKG1-AS1 (HGNC:45029): (PRKG1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012242.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DKK1	NM_012242.4	MANE Select	c.46_48delATGinsCTC	p.Met16Leu	missense	N/A	NP_036374.1	I1W660

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DKK1	ENST00000373970.4	TSL:1 MANE Select	c.46_48delATGinsCTC	p.Met16Leu	missense	N/A	ENSP00000363081.3	O94907
	PRKG1-AS1	ENST00000452247.8	TSL:5	n.23_25delCATinsGAG		non_coding_transcript_exon	Exon 1 of 7
	PRKG1-AS1	ENST00000649494.1		n.26_28delCATinsGAG		non_coding_transcript_exon	Exon 1 of 8

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.5

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr10-54074240;