chr2-218891661-C-T

Variant names:

• chr2-218891661-C-T
• rs7349332
• NM_025216.3:c.757-1113C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_025216.3(WNT10A):​c.757-1113C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,178 control chromosomes in the GnomAD database, including 1,322 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 (1322 hom., cov: 32)
• Consequence: WNT10A NM_025216.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.773
• Publications: 49 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT10A	NM_025216.3	c.757-1113C>T		intron_variant	Intron 3 of 3	ENST00000258411.8	NP_079492.2
WNT10A	XM_011511929.3	c.661-1113C>T		intron_variant	Intron 4 of 4		XP_011510231.1
WNT10A	XM_011511930.2	c.377-1113C>T		intron_variant	Intron 2 of 2		XP_011510232.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT10A	ENST00000258411.8	c.757-1113C>T		intron_variant	Intron 3 of 3	1	NM_025216.3	ENSP00000258411.3
WNT10A	ENST00000458582.1	c.263-1113C>T		intron_variant	Intron 1 of 1	3		ENSP00000388812.1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19315 AN: 152060 Hom.: 1314 Cov.: 32

Gnomad AFR AF: 0.0927

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.127 AC: 19333 AN: 152178 Hom.: 1322 Cov.: 32 AF XY: 0.127 AC XY: 9455 AN XY: 74384

African (AFR) AF: 0.0927 AC: 3849 AN: 41518

American (AMR) AF: 0.135 AC: 2073 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 403 AN: 3472

East Asian (EAS) AF: 0.225 AC: 1163 AN: 5164

South Asian (SAS) AF: 0.219 AC: 1056 AN: 4816

European-Finnish (FIN) AF: 0.105 AC: 1113 AN: 10586

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.136 AC: 9242 AN: 68002

Other (OTH) AF: 0.142 AC: 300 AN: 2114

Alfa AF: 0.137 Hom.: 5362

Bravo AF: 0.127

Asia WGS AF: 0.257 AC: 891 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	20
DANN	Benign	0.86
PhyloP100		0.77
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: rs7349332; hg19: chr2-219756383;