Variant rs2908004 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_057168.2(WNT16):c.244G>A(p.Gly82Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 1,612,998 control chromosomes in the GnomAD database, including 175,541 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. 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 Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.55 ( 25439 hom., cov: 33)

Exomes 𝑓: 0.45 ( 150102 hom. )

Consequence

WNT16
NM_057168.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.795

Variant links:

Genes affected

WNT16 (HGNC:16267): (Wnt family member 16) The WNT gene family consists of structurally related genes which encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. This gene is a member of the WNT gene family. It contains two transcript variants diverging at the 5' termini. These two variants are proposed to be the products of separate promoters and not to be splice variants from a single promoter. They are differentially expressed in normal tissues, one of which (variant 2) is expressed at significant levels only in the pancreas, whereas another one (variant 1) is expressed more ubiquitously with highest levels in adult kidney, placenta, brain, heart, and spleen. [provided by RefSeq, Jul 2008]

WNT16 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.092485E-7).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT16	NM_057168.2 link	c.244G>A	p.Gly82Arg	missense_variant	Exon 2 of 4	ENST00000222462.3	NP_476509.1	Q9UBV4-1
WNT16	NM_016087.2 link	c.214G>A	p.Gly72Arg	missense_variant	Exon 2 of 4		NP_057171.2	Q9UBV4E9PH60

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT16	ENST00000222462.3 link	c.244G>A	p.Gly82Arg	missense_variant	Exon 2 of 4	1	NM_057168.2	ENSP00000222462.2		Q9UBV4-1
WNT16	ENST00000361301.6 link	c.214G>A	p.Gly72Arg	missense_variant	Exon 2 of 4	1		ENSP00000355065.2		E9PH60

Frequencies

GnomAD3 genomes

AF:

0.545

AC:

82808

AN:

151990

Hom.:

25383

Cov.:

show subpopulations

Gnomad AFR

AF:

0.844

Gnomad AMI

AF:

0.359

Gnomad AMR

AF:

0.428

Gnomad ASJ

AF:

0.461

Gnomad EAS

AF:

0.169

Gnomad SAS

AF:

0.418

Gnomad FIN

AF:

0.402

Gnomad MID

AF:

0.484

Gnomad NFE

AF:

0.456

Gnomad OTH

AF:

0.523

GnomAD3 exomes

AF:

0.445

AC:

111106

AN:

249930

Hom.:

26983

AF XY:

0.438

AC XY:

59328

AN XY:

135334

show subpopulations

Gnomad AFR exome

AF:

0.856

Gnomad AMR exome

AF:

0.405

Gnomad ASJ exome

AF:

0.451

Gnomad EAS exome

AF:

0.177

Gnomad SAS exome

AF:

0.425

Gnomad FIN exome

AF:

0.420

Gnomad NFE exome

AF:

0.450

Gnomad OTH exome

AF:

0.457

GnomAD4 exome

AF:

0.445

AC:

650229

AN:

1460890

Hom.:

150102

Cov.:

AF XY:

0.444

AC XY:

322349

AN XY:

726822

show subpopulations

Gnomad4 AFR exome

AF:

0.864

Gnomad4 AMR exome

AF:

0.404

Gnomad4 ASJ exome

AF:

0.456

Gnomad4 EAS exome

AF:

0.151

Gnomad4 SAS exome

AF:

0.421

Gnomad4 FIN exome

AF:

0.421

Gnomad4 NFE exome

AF:

0.447

Gnomad4 OTH exome

AF:

0.453

GnomAD4 genome

AF:

0.545

AC:

82920

AN:

152108

Hom.:

25439

Cov.:

AF XY:

0.534

AC XY:

39715

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.844

Gnomad4 AMR

AF:

0.427

Gnomad4 ASJ

AF:

0.461

Gnomad4 EAS

AF:

0.169

Gnomad4 SAS

AF:

0.417

Gnomad4 FIN

AF:

0.402

Gnomad4 NFE

AF:

0.456

Gnomad4 OTH

AF:

0.526

Alfa

AF:

0.458

Hom.:

23926

Bravo

AF:

0.560

TwinsUK

AF:

0.420

AC:

1558

ALSPAC

AF:

0.442

AC:

1705

ESP6500AA

AF:

0.838

AC:

3692

ESP6500EA

AF:

0.455

AC:

3913

ExAC

AF:

0.456

AC:

55339

Asia WGS

AF:

0.368

AC:

1280

AN:

3478

EpiCase

AF:

0.454

EpiControl

AF:

0.448

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.35

.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.34

T;T

MetaRNN

Benign

9.1e-7

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-1.7

.;N

PrimateAI

Benign

0.41

PROVEAN

Benign

3.0

N;N

REVEL

Benign

0.17

Sift

Benign

0.30

T;T

Sift4G

Benign

0.26

T;T

Polyphen

0.0010

B;B

Vest4

0.13

MutPred

0.27

.;Gain of MoRF binding (P = 0.0045);

MPC

0.18

ClinPred

0.014

GERP RS

-0.77

Varity_R

0.18

gMVP

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over