Variant chr1-112509309-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_024494.3(WNT2B):c.47G>C(p.Arg16Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000173 in 1,563,500 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

WNT2B
NM_024494.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.05

Variant links:

Genes affected

WNT2B (HGNC:12781): (Wnt family member 2B) This gene encodes a member of the wingless-type MMTV integration site (WNT) family of highly conserved, secreted signaling factors. WNT family members function in a variety of developmental processes including regulation of cell growth and differentiation and are characterized by a WNT-core domain. This gene may play a role in human development as well as carcinogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

WNT2B 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
WNT2B	NM_024494.3 linkuse as main transcript	c.47G>C	p.Arg16Pro	missense_variant	1/5	ENST00000369684.5
WNT2B	NM_001291880.1 linkuse as main transcript	c.-94-5565G>C		intron_variant
WNT2B	NM_004185.4 linkuse as main transcript	c.126-5565G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNT2B	ENST00000369684.5 linkuse as main transcript	c.47G>C	p.Arg16Pro	missense_variant	1/5	1	NM_024494.3	P1	Q93097-1
WNT2B	ENST00000369686.9 linkuse as main transcript	c.126-5565G>C		intron_variant		1			Q93097-2
WNT2B	ENST00000256640.9 linkuse as main transcript	c.-94-5565G>C		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152044

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000177

AC:

AN:

1411456

Hom.:

Cov.:

AF XY:

0.0000214

AC XY:

AN XY:

699854

show subpopulations

Gnomad4 AFR exome

AF:

0.0000321

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000210

Gnomad4 OTH exome

AF:

0.0000171

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152044

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74254

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 22, 2022

This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 16 of the WNT2B protein (p.Arg16Pro). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with WNT2B-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

0.010

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.30

Eigen

Benign

-0.038

Eigen_PC

Benign

0.024

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.62

M_CAP

Pathogenic

0.33

MetaRNN

Uncertain

0.61

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

MutationTaster

Benign

0.57

D;D;D

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.040

REVEL

Uncertain

0.32

Sift

Benign

0.088

Sift4G

Pathogenic

0.0

Polyphen

0.93

Vest4

0.47

MutPred

0.15

Gain of loop (P = 0.0045);

MVP

0.65

MPC

1.3

ClinPred

0.87

GERP RS

3.9

Varity_R

0.25

gMVP

0.64

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over