Genetic Variant NM_024494.3:c.62C>T (chr1-112509324-C-T) – 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.62C>T(p.Pro21Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000035 in 1,429,400 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. 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. P21R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

WNT2B
NM_024494.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.119

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=0.11409366).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT2B	NM_024494.3 link	c.62C>T	p.Pro21Leu	missense_variant	Exon 1 of 5	ENST00000369684.5	NP_078613.1	Q93097-1
WNT2B	NM_004185.4 link	c.126-5550C>T		intron_variant	Intron 2 of 5		NP_004176.2	Q93097-2
WNT2B	NM_001291880.1 link	c.-94-5550C>T		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.62C>T	p.Pro21Leu	missense_variant	Exon 1 of 5	1	NM_024494.3	ENSP00000358698.4	Q93097-1
WNT2B	ENST00000369686.9 link	c.126-5550C>T		intron_variant	Intron 2 of 5	1		ENSP00000358700.4	Q93097-2
WNT2B	ENST00000256640.9 link	c.-94-5550C>T		intron_variant	Intron 1 of 4	2		ENSP00000256640.5	Q5TEH8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000153

AC:

AN:

196468

AF XY:

0.00000912

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:

0.00

Gnomad NFE exome

AF:

0.0000347

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000350

AC:

AN:

1429400

Hom.:

Cov.:

AF XY:

0.00000282

AC XY:

AN XY:

710270

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31588

American (AMR)

AF:

0.00

AC:

AN:

41468

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25472

East Asian (EAS)

AF:

0.00

AC:

AN:

38200

South Asian (SAS)

AF:

0.00

AC:

AN:

83928

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42890

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4116

European-Non Finnish (NFE)

AF:

0.00000454

AC:

AN:

1102510

Other (OTH)

AF:

0.00

AC:

AN:

59228

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.535

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000255

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.56

M_CAP

Pathogenic

0.31

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

-0.12

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.71

REVEL

Benign

0.10

Sift

Uncertain

0.022

Sift4G

Uncertain

0.029

Polyphen

0.0090

Vest4

0.11

MutPred

0.17

Loss of relative solvent accessibility (P = 0.0306);

MVP

0.62

MPC

1.3

ClinPred

0.11

GERP RS

2.2

PromoterAI

-0.012

Neutral

(source)

Varity_R

0.034

gMVP

0.51

Mutation Taster

=92/8

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over