NM_025216.3:c.114-322T>C

Variant names:

• chr2-218881839-T-C
• rs10177996
• NM_025216.3:c.114-322T>C

Variant summary

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

The NM_025216.3(WNT10A):​c.114-322T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 152,022 control chromosomes in the GnomAD database, including 13,854 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 0.35 (13854 hom., cov: 32)
• Consequence: WNT10A NM_025216.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• Publications: 24 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT10A	NM_025216.3	c.114-322T>C		intron_variant	Intron 1 of 3	ENST00000258411.8	NP_079492.2
WNT10A	XM_011511929.3	c.18-322T>C		intron_variant	Intron 2 of 4		XP_011510231.1
WNT10A	XM_011511930.2	c.114-322T>C		intron_variant	Intron 1 of 2		XP_011510232.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT10A	ENST00000258411.8	c.114-322T>C		intron_variant	Intron 1 of 3	1	NM_025216.3	ENSP00000258411.3

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53503 AN: 151904 Hom.: 13805 Cov.: 32

Gnomad AFR AF: 0.735

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.315

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

GnomAD4 genome AF: 0.353 AC: 53609 AN: 152022 Hom.: 13854 Cov.: 32 AF XY: 0.348 AC XY: 25885 AN XY: 74316

African (AFR) AF: 0.735 AC: 30443 AN: 41418

American (AMR) AF: 0.268 AC: 4090 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 574 AN: 3466

East Asian (EAS) AF: 0.264 AC: 1364 AN: 5160

South Asian (SAS) AF: 0.306 AC: 1475 AN: 4820

European-Finnish (FIN) AF: 0.188 AC: 1986 AN: 10592

Middle Eastern (MID) AF: 0.226 AC: 66 AN: 292

European-Non Finnish (NFE) AF: 0.188 AC: 12793 AN: 67978

Other (OTH) AF: 0.320 AC: 675 AN: 2110

Alfa AF: 0.231 Hom.: 23646

Bravo AF: 0.372

Asia WGS AF: 0.369 AC: 1281 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.6
DANN	Benign	0.59
PhyloP100		-1.3
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: rs10177996; hg19: chr2-219746561;