Variant 5-1035404-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_033120.4(NKD2):c.590G>A(p.Arg197His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00303 in 1,558,670 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0036 ( 3 hom., cov: 34)

Exomes 𝑓: 0.0030 ( 31 hom. )

Consequence

NKD2
NM_033120.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.361

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0036799312).

BP6

Variant 5-1035404-G-A is Benign according to our data. Variant chr5-1035404-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 778317.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NKD2	NM_033120.4 linkuse as main transcript	c.590G>A	p.Arg197His	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.590G>A	p.Arg197His	missense_variant	8/10	1	NM_033120.4	P2	Q969F2-1
NKD2	ENST00000274150.4 linkuse as main transcript	c.590G>A	p.Arg197His	missense_variant	8/11	1		A2	Q969F2-2
NKD2	ENST00000519933.5 linkuse as main transcript	n.359G>A		non_coding_transcript_exon_variant	3/4	2
NKD2	ENST00000523688.1 linkuse as main transcript	n.164G>A		non_coding_transcript_exon_variant	2/4	3

Frequencies

GnomAD3 genomes

AF:

0.00358

AC:

545

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000434

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00248

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000413

Gnomad FIN

AF:

0.0245

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00323

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.00392

AC:

662

AN:

168944

Hom.:

AF XY:

0.00357

AC XY:

319

AN XY:

89350

show subpopulations

Gnomad AFR exome

AF:

0.000614

Gnomad AMR exome

AF:

0.00150

Gnomad ASJ exome

AF:

0.000115

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000258

Gnomad FIN exome

AF:

0.0248

Gnomad NFE exome

AF:

0.00299

Gnomad OTH exome

AF:

0.00259

GnomAD4 exome

AF:

0.00297

AC:

4175

AN:

1406298

Hom.:

Cov.:

AF XY:

0.00289

AC XY:

2007

AN XY:

694384

show subpopulations

Gnomad4 AFR exome

AF:

0.000313

Gnomad4 AMR exome

AF:

0.00149

Gnomad4 ASJ exome

AF:

0.0000396

Gnomad4 EAS exome

AF:

0.000193

Gnomad4 SAS exome

AF:

0.000201

Gnomad4 FIN exome

AF:

0.0235

Gnomad4 NFE exome

AF:

0.00254

Gnomad4 OTH exome

AF:

0.00307

GnomAD4 genome

AF:

0.00358

AC:

545

AN:

152372

Hom.:

Cov.:

AF XY:

0.00435

AC XY:

324

AN XY:

74518

show subpopulations

Gnomad4 AFR

AF:

0.000433

Gnomad4 AMR

AF:

0.00248

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.0245

Gnomad4 NFE

AF:

0.00323

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00235

Hom.:

Bravo

AF:

0.00156

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000691

AC:

ESP6500EA

AF:

0.00187

AC:

ExAC

AF:

0.00193

AC:

222

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2022	NKD2: BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jun 28, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Uncertain

0.57

D;.

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.74

T;T

MetaRNN

Benign

0.0037

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.6

L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-2.5

D;D

REVEL

Benign

0.12

Sift

Benign

0.10

T;T

Sift4G

Benign

0.12

T;T

Polyphen

0.022

B;B

Vest4

0.18

MVP

0.63

MPC

0.051

ClinPred

0.013

GERP RS

2.9

Varity_R

0.064

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over