5-1035391-CGG-GGC

Variant names:

• chr5-1035391-CGG-GGC
• NM_033120.4:c.577_579delCGGinsGGC
• NKD2 p.Arg193Gly

Variant summary

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

The NM_033120.4(NKD2):​c.577_579delCGGinsGGC​(p.Arg193Gly) variant causes a missense, splice region 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R193Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: NKD2 NM_033120.4 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.15
• Publications: 0 publications found

Genes affected

NKD2 (HGNC:17046): (NKD inhibitor of WNT signaling pathway 2) This gene encodes a member of a family of proteins that function as negative regulators of Wnt receptor signaling through interaction with Dishevelled family members. The encoded protein participates in the delivery of transforming growth factor alpha-containing vesicles to the cell membrane. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2012]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033120.4. 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
	NKD2	NM_033120.4	MANE Select	c.577_579delCGGinsGGC	p.Arg193Gly	missense splice_region	N/A	NP_149111.1	Q969F2-1
	NKD2	NM_001271082.2		c.577_579delCGGinsGGC	p.Arg193Gly	missense splice_region	N/A	NP_001258011.1	Q969F2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NKD2	ENST00000296849.10	TSL:1 MANE Select	c.577_579delCGGinsGGC	p.Arg193Gly	missense splice_region	N/A	ENSP00000296849.5	Q969F2-1
	NKD2	ENST00000274150.4	TSL:1	c.577_579delCGGinsGGC	p.Arg193Gly	missense splice_region	N/A	ENSP00000274150.4	Q969F2-2
	NKD2	ENST00000866687.1		c.577_579delCGGinsGGC	p.Arg193Gly	missense splice_region	N/A	ENSP00000536746.1

Frequencies

GnomAD3 genomes Cov.: 34

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

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.1

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: chr5-1035506;