2-218880997-T-G

Variant names:

• chr2-218880997-T-G
• NM_025216.3:c.2T>G

Variant summary

Our verdict is Pathogenic. The variant received 13 ACMG points: 13P and 0B. PVS1 PS1_Moderate PM2 PP5

The NM_025216.3(WNT10A):​c.2T>G​(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: WNT10A NM_025216.3 start_lost
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.737
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• ectodermal dysplasia WNT10A related

  Inheritance: SD Classification: DEFINITIVE Submitted by: ClinGen, Illumina
• tooth agenesis, selective, 4

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• odonto-onycho-dermal dysplasia

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
• Schöpf-Schulz-Passarge syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• tooth agenesis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal recessive hypohidrotic ectodermal dysplasia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000300702 (HGNC:):

ACMG classification

Our verdict: Pathogenic. The variant received 13 ACMG points.

• PVS1: Start lost variant, next in-frame start position is after 14 pathogenic variants. Next in-frame start position is after 36 codons. Genomic position: 218881101. Lost 0.085 part of the original CDS.
• PS1: Another start lost variant in NM_025216.3 (WNT10A) was described as [Likely_pathogenic] in ClinVar as 1466056
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 2-218880997-T-G is Pathogenic according to our data. Variant chr2-218880997-T-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 4063347.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT10A	NM_025216.3	c.2T>G	p.Met1?	start_lost	Exon 1 of 4	ENST00000258411.8	NP_079492.2
WNT10A	XM_011511930.2	c.2T>G	p.Met1?	start_lost	Exon 1 of 3		XP_011510232.1
WNT10A	XM_011511929.3	c.18-1164T>G		intron_variant	Intron 2 of 4		XP_011510231.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT10A	ENST00000258411.8	c.2T>G	p.Met1?	start_lost	Exon 1 of 4	1	NM_025216.3	ENSP00000258411.3
ENSG00000300702	ENST00000773519.1	n.*149T>G		downstream_gene_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Schöpf-Schulz-Passarge syndrome Pathogenic:1

May 27, 2025

Natera, Inc.

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.63	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	23
DANN	Benign	0.93
DEOGEN2	Benign	0.043	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.66	D
LIST_S2	Uncertain	0.90	D
M_CAP	Pathogenic	0.78	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Benign	-0.79	T
PhyloP100		0.74
PROVEAN	Benign	-0.62	N
REVEL	Uncertain	0.41
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.0	B
Vest4		0.81
MutPred		0.95		Gain of methylation at M1 (P = 0.0017);
MVP		0.73
ClinPred		0.81	D
GERP RS		2.3
PromoterAI		-0.051	Neutral
Varity_R		0.93
gMVP		0.72
Mutation Taster		=20/180	disease causing

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

Other links and lift over

hg19: chr2-219745719;