1-112509287-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_024494.3(WNT2B):c.25G>A(p.Glu9Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0173 in 1,541,958 control chromosomes in the GnomAD database, including 305 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.013 ( 22 hom., cov: 33)

Exomes 𝑓: 0.018 ( 283 hom. )

Consequence

WNT2B
NM_024494.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.85

Publications

3 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia

WNT2B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003770262).

BP6

Variant 1-112509287-G-A is Benign according to our data. Variant chr1-112509287-G-A is described in ClinVar as [Benign]. Clinvar id is 1970963.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0129 (1969/152202) while in subpopulation NFE AF = 0.0196 (1334/68000). AF 95% confidence interval is 0.0187. There are 22 homozygotes in GnomAd4. There are 948 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT2B	NM_024494.3 link	c.25G>A	p.Glu9Lys	missense_variant	Exon 1 of 5	ENST00000369684.5	NP_078613.1	Q93097-1
WNT2B	NM_004185.4 link	c.126-5587G>A		intron_variant	Intron 2 of 5		NP_004176.2	Q93097-2
WNT2B	NM_001291880.1 link	c.-94-5587G>A		intron_variant	Intron 1 of 4		NP_001278809.1	Q93097Q5TEH8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
WNT2B	ENST00000369684.5 link	c.25G>A	p.Glu9Lys	missense_variant	Exon 1 of 5	1	NM_024494.3	ENSP00000358698.4	Q93097-1
WNT2B	ENST00000369686.9 link	c.126-5587G>A		intron_variant	Intron 2 of 5	1		ENSP00000358700.4	Q93097-2
WNT2B	ENST00000256640.9 link	c.-94-5587G>A		intron_variant	Intron 1 of 4	2		ENSP00000256640.5	Q5TEH8

Frequencies

GnomAD3 genomes

AF:

0.0129

AC:

1967

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00302

Gnomad AMI

AF:

0.0362

Gnomad AMR

AF:

0.0101

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.0255

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0196

Gnomad OTH

AF:

0.0105

GnomAD2 exomes

AF:

0.0122

AC:

1737

AN:

142568

AF XY:

0.0121

show subpopulations

Gnomad AFR exome

AF:

0.00251

Gnomad AMR exome

AF:

0.00808

Gnomad ASJ exome

AF:

0.00329

Gnomad EAS exome

AF:

0.0000943

Gnomad FIN exome

AF:

0.0240

Gnomad NFE exome

AF:

0.0190

Gnomad OTH exome

AF:

0.0120

GnomAD4 exome

AF:

0.0178

AC:

24695

AN:

1389756

Hom.:

283

Cov.:

AF XY:

0.0175

AC XY:

12050

AN XY:

687410

show subpopulations

African (AFR)

AF:

0.00238

AC:

AN:

30248

American (AMR)

AF:

0.00777

AC:

273

AN:

35122

Ashkenazi Jewish (ASJ)

AF:

0.00326

AC:

AN:

24550

East Asian (EAS)

AF:

0.0000281

AC:

AN:

35528

South Asian (SAS)

AF:

0.00511

AC:

409

AN:

80060

European-Finnish (FIN)

AF:

0.0232

AC:

950

AN:

40906

Middle Eastern (MID)

AF:

0.00420

AC:

AN:

4044

European-Non Finnish (NFE)

AF:

0.0203

AC:

21940

AN:

1081584

Other (OTH)

AF:

0.0165

AC:

953

AN:

57714

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1564

3129

4693

6258

7822

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0129

AC:

1969

AN:

152202

Hom.:

Cov.:

AF XY:

0.0127

AC XY:

948

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.00301

AC:

125

AN:

41546

American (AMR)

AF:

0.0101

AC:

155

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00346

AC:

AN:

3472

East Asian (EAS)

AF:

0.000195

AC:

AN:

5124

South Asian (SAS)

AF:

0.00332

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0255

AC:

271

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0196

AC:

1334

AN:

68000

Other (OTH)

AF:

0.0104

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

106

213

319

426

532

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0155

Hom.:

Bravo

AF:

0.0114

TwinsUK

AF:

0.0208

AC:

ALSPAC

AF:

0.0210

AC:

ESP6500AA

AF:

0.00353

AC:

ESP6500EA

AF:

0.0117

AC:

ExAC

AF:

0.00895

AC:

827

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.70

MetaRNN

Benign

0.0038

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

1.9

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.15

REVEL

Benign

0.26

Sift

Benign

0.52

Sift4G

Pathogenic

0.0

Polyphen

0.0010

Vest4

0.28

MPC

0.93

ClinPred

0.015

GERP RS

3.0

PromoterAI

-0.097

Neutral

(source)

Varity_R

0.091

gMVP

0.59

Mutation Taster

=100/0

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

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1-112509287-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over