Genetic Variant WNT2B:p.Gly5Arg (chr1-112509275-G-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_024494.3(WNT2B):c.13G>C(p.Gly5Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000658 in 1,534,644 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000061 ( 0 hom. )

Consequence

WNT2B
NM_024494.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: -0.266

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

diarrhea 9
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

WNT2B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.050555706).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024494.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WNT2B	NM_024494.3	MANE Select	c.13G>C	p.Gly5Arg	missense	Exon 1 of 5	NP_078613.1	Q93097-1
WNT2B	NM_004185.4		c.126-5599G>C		intron	N/A	NP_004176.2	Q93097-2
WNT2B	NM_001291880.1		c.-94-5599G>C		intron	N/A	NP_001278809.1	Q93097

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WNT2B	ENST00000369684.5	TSL:1 MANE Select	c.13G>C	p.Gly5Arg	missense	Exon 1 of 5	ENSP00000358698.4	Q93097-1
WNT2B	ENST00000369686.9	TSL:1	c.126-5599G>C		intron	N/A	ENSP00000358700.4	Q93097-2
WNT2B	ENST00000870348.1		c.13G>C	p.Gly5Arg	missense	Exon 1 of 5	ENSP00000540407.1

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00219

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:

0.000206

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000603

AC:

AN:

132648

AF XY:

0.0000544

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000107

Gnomad NFE exome

AF:

0.000115

Gnomad OTH exome

AF:

0.000271

GnomAD4 exome

AF:

0.0000608

AC:

AN:

1382456

Hom.:

Cov.:

AF XY:

0.0000629

AC XY:

AN XY:

683306

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29882

American (AMR)

AF:

0.00

AC:

AN:

34254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24394

East Asian (EAS)

AF:

0.00

AC:

AN:

34928

South Asian (SAS)

AF:

0.00

AC:

AN:

79202

European-Finnish (FIN)

AF:

0.000123

AC:

AN:

40500

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4044

European-Non Finnish (NFE)

AF:

0.0000724

AC:

AN:

1077846

Other (OTH)

AF:

0.0000174

AC:

AN:

57406

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000112

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41466

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

68028

Other (OTH)

AF:

0.000478

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000464

Hom.:

Bravo

AF:

0.0000982

ExAC

AF:

0.0000228

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.30

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.65

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.051

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

-0.27

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.43

REVEL

Benign

0.11

Sift

Benign

0.10

Sift4G

Pathogenic

0.0

Polyphen

0.0

Vest4

0.16

MutPred

0.19

Gain of MoRF binding (P = 0.0051)

MVP

0.79

MPC

1.7

ClinPred

0.51

GERP RS

0.86

PromoterAI

-0.17

Neutral

(source)

Varity_R

0.054

gMVP

0.52

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over