dbSNP rs564238232: WNT2B:p.Pro23Thr (chr1-112509329-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024494.3(WNT2B):c.67C>A(p.Pro23Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000697 in 1,434,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. P23S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

WNT2B
NM_024494.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.811

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

WNT2B links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09891507).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT2B	NM_024494.3 link	c.67C>A	p.Pro23Thr	missense_variant	Exon 1 of 5	ENST00000369684.5	NP_078613.1	Q93097-1
WNT2B	NM_004185.4 link	c.126-5545C>A		intron_variant	Intron 2 of 5		NP_004176.2	Q93097-2
WNT2B	NM_001291880.1 link	c.-94-5545C>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.67C>A	p.Pro23Thr	missense_variant	Exon 1 of 5	1	NM_024494.3	ENSP00000358698.4	Q93097-1
WNT2B	ENST00000369686.9 link	c.126-5545C>A		intron_variant	Intron 2 of 5	1		ENSP00000358700.4	Q93097-2
WNT2B	ENST00000256640.9 link	c.-94-5545C>A		intron_variant	Intron 1 of 4	2		ENSP00000256640.5	Q5TEH8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.97e-7

AC:

AN:

1434996

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

713696

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31750

American (AMR)

AF:

0.00

AC:

AN:

42482

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25586

East Asian (EAS)

AF:

0.00

AC:

AN:

38416

South Asian (SAS)

AF:

0.00

AC:

AN:

84390

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43340

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4134

European-Non Finnish (NFE)

AF:

9.05e-7

AC:

AN:

1105434

Other (OTH)

AF:

0.00

AC:

AN:

59464

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.30

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.52

M_CAP

Benign

0.035

MetaRNN

Benign

0.099

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

0.81

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.44

REVEL

Benign

0.097

Sift

Benign

0.24

Sift4G

Benign

0.25

Polyphen

0.0050

Vest4

0.27

MutPred

0.21

Gain of phosphorylation at P23 (P = 0.0148);

MVP

0.46

MPC

1.3

ClinPred

0.092

GERP RS

1.2

PromoterAI

-0.012

Neutral

(source)

Varity_R

0.053

gMVP

0.55

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

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rs564238232

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over