rs74333950

Variant names:

• chr2-218881570-T-G
• rs74333950
• NM_025216.3:c.113+462T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025216.3(WNT10A):​c.113+462T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 139,300 control chromosomes in the GnomAD database, including 1,174 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (1174 hom., cov: 32)
• Consequence: WNT10A NM_025216.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0560
• Publications: 10 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025216.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT10A	NM_025216.3	MANE Select	c.113+462T>G		intron	N/A	NP_079492.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT10A	ENST00000258411.8	TSL:1 MANE Select	c.113+462T>G		intron	N/A	ENSP00000258411.3

Frequencies

GnomAD3 genomes AF: 0.132 AC: 18316 AN: 139208 Hom.: 1172 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.125

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.132

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.132 AC: 18318 AN: 139300 Hom.: 1174 Cov.: 32 AF XY: 0.131 AC XY: 8917 AN XY: 68052

African (AFR) AF: 0.111 AC: 3725 AN: 33434

American (AMR) AF: 0.109 AC: 1492 AN: 13630

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 380 AN: 3404

East Asian (EAS) AF: 0.211 AC: 1074 AN: 5102

South Asian (SAS) AF: 0.215 AC: 994 AN: 4620

European-Finnish (FIN) AF: 0.108 AC: 1086 AN: 10040

Middle Eastern (MID) AF: 0.113 AC: 32 AN: 284

European-Non Finnish (NFE) AF: 0.139 AC: 9175 AN: 65964

Other (OTH) AF: 0.134 AC: 259 AN: 1940

Alfa AF: 0.145 Hom.: 606

Bravo AF: 0.164

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.3
DANN	Benign	0.37
PhyloP100		-0.056
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs74333950; hg19: chr2-219746292;