Variant chr5-1034760-T-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.431T>A(p.Met144Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00183 in 1,610,730 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0053 ( 7 hom., cov: 33)

Exomes 𝑓: 0.0015 ( 25 hom. )

Consequence

NKD2
NM_033120.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.73

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=0.0098873675).

BP6

Variant 5-1034760-T-A is Benign according to our data. Variant chr5-1034760-T-A is described in ClinVar as [Benign]. Clinvar id is 781623.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NKD2	NM_033120.4 linkuse as main transcript	c.431T>A	p.Met144Lys	missense_variant	7/10	ENST00000296849.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NKD2	ENST00000296849.10 linkuse as main transcript	c.431T>A	p.Met144Lys	missense_variant	7/10	1	NM_033120.4	P2	Q969F2-1
NKD2	ENST00000274150.4 linkuse as main transcript	c.431T>A	p.Met144Lys	missense_variant	7/11	1		A2	Q969F2-2
NKD2	ENST00000519933.5 linkuse as main transcript	n.200T>A		non_coding_transcript_exon_variant	2/4	2
NKD2	ENST00000523688.1 linkuse as main transcript	n.5T>A		non_coding_transcript_exon_variant	1/4	3

Frequencies

GnomAD3 genomes

AF:

0.00532

AC:

810

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0124

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00700

Gnomad ASJ

AF:

0.0381

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000588

Gnomad OTH

AF:

0.00717

GnomAD3 exomes

AF:

0.00289

AC:

720

AN:

249198

Hom.:

AF XY:

0.00246

AC XY:

332

AN XY:

135214

show subpopulations

Gnomad AFR exome

AF:

0.0133

Gnomad AMR exome

AF:

0.00269

Gnomad ASJ exome

AF:

0.0314

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000634

Gnomad OTH exome

AF:

0.00460

GnomAD4 exome

AF:

0.00147

AC:

2143

AN:

1458426

Hom.:

Cov.:

AF XY:

0.00140

AC XY:

1014

AN XY:

725064

show subpopulations

Gnomad4 AFR exome

AF:

0.0138

Gnomad4 AMR exome

AF:

0.00376

Gnomad4 ASJ exome

AF:

0.0312

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000397

Gnomad4 OTH exome

AF:

0.00390

GnomAD4 genome

AF:

0.00532

AC:

811

AN:

152304

Hom.:

Cov.:

AF XY:

0.00509

AC XY:

379

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0123

Gnomad4 AMR

AF:

0.00699

Gnomad4 ASJ

AF:

0.0381

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000588

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00529

Hom.:

Bravo

AF:

0.00666

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00954

AC:

ESP6500EA

AF:

0.00267

AC:

ExAC

AF:

0.00260

AC:

315

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00109

EpiControl

AF:

0.00136

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	May 18, 2018	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2023	NKD2: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.93

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Uncertain

0.020

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Uncertain

0.64

D;.

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.85

D;D

MetaRNN

Benign

0.0099

T;T

MetaSVM

Benign

-0.49

MutationAssessor

Uncertain

2.8

M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.43

PROVEAN

Pathogenic

-4.9

D;D

REVEL

Benign

0.27

Sift

Benign

0.080

T;T

Sift4G

Benign

0.17

T;T

Polyphen

0.98

D;P

Vest4

0.87

MVP

0.59

MPC

0.34

ClinPred

0.066

GERP RS

3.2

Varity_R

0.75

gMVP

0.95

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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