Variant 5-1035392-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_033120.4(NKD2):c.578G>A(p.Arg193Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000899 in 1,557,056 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R193W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000085 ( 0 hom. )

Consequence

NKD2
NM_033120.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.355

Variant links:

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]

NKD2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NKD2	NM_033120.4 linkuse as main transcript	c.578G>A	p.Arg193Gln	missense_variant	8/10	ENST00000296849.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NKD2	ENST00000296849.10 linkuse as main transcript	c.578G>A	p.Arg193Gln	missense_variant	8/10	1	NM_033120.4	P2	Q969F2-1
NKD2	ENST00000274150.4 linkuse as main transcript	c.578G>A	p.Arg193Gln	missense_variant	8/11	1		A2	Q969F2-2
NKD2	ENST00000519933.5 linkuse as main transcript	n.347G>A		non_coding_transcript_exon_variant	3/4	2
NKD2	ENST00000523688.1 linkuse as main transcript	n.152G>A		non_coding_transcript_exon_variant	2/4	3

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000240

AC:

AN:

166854

Hom.:

AF XY:

0.0000227

AC XY:

AN XY:

88106

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000387

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000818

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000631

Gnomad NFE exome

AF:

0.0000149

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000854

AC:

AN:

1404818

Hom.:

Cov.:

AF XY:

0.00000721

AC XY:

AN XY:

693448

show subpopulations

Gnomad4 AFR exome

AF:

0.0000313

Gnomad4 AMR exome

AF:

0.0000272

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000276

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000204

Gnomad4 NFE exome

AF:

0.00000739

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000149

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000350

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.031

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.40

T;.

Eigen

Benign

0.059

Eigen_PC

Benign

-0.043

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.73

T;T

M_CAP

Benign

0.031

MetaRNN

Benign

0.010

T;T

MetaSVM

Benign

-0.76

MutationAssessor

Uncertain

2.7

M;M

MutationTaster

Benign

0.93

D;D;D

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-2.2

N;N

REVEL

Benign

0.21

Sift

Benign

0.15

T;T

Sift4G

Benign

0.51

T;T

Polyphen

0.99

D;D

Vest4

0.16

MVP

0.69

MPC

0.057

ClinPred

0.36

GERP RS

2.9

Varity_R

0.10

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.27

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.27

Position offset: 2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over