chr2-218893145-C-G

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP3_Strong

The NM_025216.3(WNT10A):​c.1128C>G​(p.Cys376Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging 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. C376F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

WNT10A
NM_025216.3 missense

Scores

17
1
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.65
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

PM1
In a disulfide_bond (size 31) in uniprot entity WN10A_HUMAN there are 9 pathogenic changes around while only 0 benign (100%) in NM_025216.3
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.986

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
WNT10ANM_025216.3 linkc.1128C>G p.Cys376Trp missense_variant Exon 4 of 4 ENST00000258411.8 NP_079492.2 Q9GZT5A0A2K8FR47
WNT10AXM_011511929.3 linkc.1032C>G p.Cys344Trp missense_variant Exon 5 of 5 XP_011510231.1
WNT10AXM_011511930.2 linkc.748C>G p.Leu250Val missense_variant Exon 3 of 3 XP_011510232.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
WNT10AENST00000258411.8 linkc.1128C>G p.Cys376Trp missense_variant Exon 4 of 4 1 NM_025216.3 ENSP00000258411.3 Q9GZT5
WNT10AENST00000458582.1 linkc.634C>G p.???212??? splice_region_variant, synonymous_variant Exon 2 of 2 3 ENSP00000388812.1 H7BZB8
WNT10AENST00000489887.1 linkn.-76C>G upstream_gene_variant 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.48
D
BayesDel_noAF
Pathogenic
0.46
CADD
Pathogenic
32
DANN
Uncertain
0.99
DEOGEN2
Pathogenic
0.91
D
Eigen
Pathogenic
0.85
Eigen_PC
Pathogenic
0.73
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Pathogenic
0.97
D
M_CAP
Pathogenic
0.95
D
MetaRNN
Pathogenic
0.99
D
MetaSVM
Pathogenic
1.0
D
MutationAssessor
Pathogenic
4.0
H
PrimateAI
Pathogenic
0.86
D
PROVEAN
Pathogenic
-10
D
REVEL
Pathogenic
0.94
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.87
MutPred
0.86
Loss of disorder (P = 0.0225);
MVP
0.98
MPC
2.4
ClinPred
1.0
D
GERP RS
4.0
Varity_R
0.94
gMVP
0.97

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-219757867; API