Genetic Variant NM_024494.3:c.23A>T (chr1-112509285-A-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_024494.3(WNT2B):c.23A>T(p.Glu8Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,388,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. E8A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

WNT2B
NM_024494.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.39

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26940235).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT2B	NM_024494.3 link	c.23A>T	p.Glu8Val	missense_variant	Exon 1 of 5	ENST00000369684.5	NP_078613.1	Q93097-1
WNT2B	NM_004185.4 link	c.126-5589A>T		intron_variant	Intron 2 of 5		NP_004176.2	Q93097-2
WNT2B	NM_001291880.1 link	c.-94-5589A>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.23A>T	p.Glu8Val	missense_variant	Exon 1 of 5	1	NM_024494.3	ENSP00000358698.4	Q93097-1
WNT2B	ENST00000369686.9 link	c.126-5589A>T		intron_variant	Intron 2 of 5	1		ENSP00000358700.4	Q93097-2
WNT2B	ENST00000256640.9 link	c.-94-5589A>T		intron_variant	Intron 1 of 4	2		ENSP00000256640.5	Q5TEH8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000144

AC:

AN:

1388848

Hom.:

Cov.:

AF XY:

0.00000291

AC XY:

AN XY:

686896

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30228

American (AMR)

AF:

0.00

AC:

AN:

35044

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24536

East Asian (EAS)

AF:

0.00

AC:

AN:

35456

South Asian (SAS)

AF:

0.00

AC:

AN:

79948

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40890

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4040

European-Non Finnish (NFE)

AF:

0.00000185

AC:

AN:

1081034

Other (OTH)

AF:

0.00

AC:

AN:

57672

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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

0.14

BayesDel_addAF

Benign

-0.030

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.33

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.63

M_CAP

Pathogenic

0.31

MetaRNN

Benign

0.27

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.0

PhyloP100

1.4

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.57

REVEL

Uncertain

0.30

Sift

Benign

0.050

Sift4G

Pathogenic

0.0

Polyphen

0.022

Vest4

0.40

MutPred

0.16

Gain of MoRF binding (P = 0.0134);

MVP

0.91

MPC

1.1

ClinPred

0.85

GERP RS

3.9

PromoterAI

-0.064

Neutral

(source)

Varity_R

0.15

gMVP

0.69

Mutation Taster

=88/12

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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NM_024494.3:c.23A>T

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