Variant 2-218890332-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PM5PP3_Strong

The ENST00000258411.8(WNT10A):c.725T>A(p.Met242Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,236 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. M242R) has been classified as Likely pathogenic.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

WNT10A
ENST00000258411.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.09

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr2-218890332-T-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 520967.Status of the report is criteria_provided_single_submitter, 1 stars.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.96

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
WNT10A	NM_025216.3 linkuse as main transcript	c.725T>A	p.Met242Lys	missense_variant	3/4	ENST00000258411.8	NP_079492.2
WNT10A	XM_011511929.3 linkuse as main transcript	c.629T>A	p.Met210Lys	missense_variant	4/5		XP_011510231.1
WNT10A	XM_011511930.2 linkuse as main transcript	c.377-2442T>A		intron_variant			XP_011510232.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WNT10A	ENST00000258411.8 linkuse as main transcript	c.725T>A	p.Met242Lys	missense_variant	3/4	1	NM_025216.3	ENSP00000258411	P1
WNT10A	ENST00000458582.1 linkuse as main transcript	c.264-2442T>A		intron_variant		3		ENSP00000388812

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000420

AC:

AN:

238368

Hom.:

AF XY:

0.00000768

AC XY:

AN XY:

130268

show subpopulations

Gnomad AFR exome

AF:

0.0000659

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000827

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Pathogenic

0.31

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.89

Eigen

Pathogenic

0.74

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.94

M_CAP

Pathogenic

0.34

MetaRNN

Pathogenic

0.96

MetaSVM

Uncertain

0.59

MutationAssessor

Pathogenic

4.0

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.90

PROVEAN

Uncertain

-4.0

REVEL

Pathogenic

0.90

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.0070

Polyphen

0.99

Vest4

0.93

MutPred

0.86

Loss of stability (P = 0.0245);

MVP

0.96

MPC

0.26

ClinPred

0.99

GERP RS

4.5

Varity_R

0.94

gMVP

0.91

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over