2-218881002-A-T

Position:

chr2-218881002-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_025216.3(WNT10A):c.7A>T(p.Ser3Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000888 in 1,576,392 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000084 ( 0 hom. )

Consequence

WNT10A
NM_025216.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.13

Variant links:

Genes affected

WNT10A (HGNC:13829): (Wnt family member 10A) The WNT gene family consists of structurally related genes which encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. This gene is a member of the WNT gene family. It is strongly expressed in the cell lines of promyelocytic leukemia and Burkitt's lymphoma. In addition, it and another family member, the WNT6 gene, are strongly coexpressed in colorectal cancer cell lines. The gene overexpression may play key roles in carcinogenesis through activation of the WNT-beta-catenin-TCF signaling pathway. This gene and the WNT6 gene are clustered in the chromosome 2q35 region. [provided by RefSeq, Jul 2008]

WNT10A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29596984).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
WNT10A	NM_025216.3 linkuse as main transcript	c.7A>T	p.Ser3Cys	missense_variant	1/4	ENST00000258411.8	NP_079492.2
WNT10A	XM_011511930.2 linkuse as main transcript	c.7A>T	p.Ser3Cys	missense_variant	1/3		XP_011510232.1
WNT10A	XM_011511929.3 linkuse as main transcript	c.18-1159A>T		intron_variant			XP_011510231.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WNT10A	ENST00000258411.8 linkuse as main transcript	c.7A>T	p.Ser3Cys	missense_variant	1/4	1	NM_025216.3	ENSP00000258411	P1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000557

AC:

AN:

179662

Hom.:

AF XY:

0.0000101

AC XY:

AN XY:

98602

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000139

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000843

AC:

AN:

1424316

Hom.:

Cov.:

AF XY:

0.00000851

AC XY:

AN XY:

705050

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000110

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152076

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000283

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Odonto-onycho-dermal dysplasia;C1835492:Tooth agenesis, selective, 4

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 01, 2021

This sequence change replaces serine with cysteine at codon 3 of the WNT10A protein (p.Ser3Cys). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and cysteine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has not been reported in the literature in individuals affected with WNT10A-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.0037

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

DANN

Benign

0.92

DEOGEN2

Benign

0.057

Eigen

Benign

-0.041

Eigen_PC

Benign

-0.015

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.48

M_CAP

Uncertain

0.24

MetaRNN

Benign

0.30

MetaSVM

Benign

-0.69

MutationAssessor

Benign

0.0

MutationTaster

Benign

0.94

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.84

REVEL

Uncertain

0.29

Sift

Benign

0.030

Sift4G

Benign

0.11

Polyphen

0.84

Vest4

0.40

MutPred

0.29

Gain of catalytic residue at M1 (P = 0.0071);

MVP

0.86

MPC

0.070

ClinPred

0.35

GERP RS

3.5

Varity_R

0.13

gMVP

0.64

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over