rs115839019

Variant names:

• chr2-218881080-C-T
• rs115839019
• NM_025216.3:c.85C>T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_025216.3(WNT10A):​c.85C>T​(p.Leu29Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00154 in 1,604,828 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0089 (19 hom., cov: 32)
  • Exomes 𝑓: 0.00078 (11 hom.)
• Consequence: WNT10A NM_025216.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.09

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]

ACMG classification

Verdict is Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 2-218881080-C-T is Benign according to our data. Variant chr2-218881080-C-T is described in ClinVar as [Benign]. Clinvar id is 334392.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00887 (1351/152350) while in subpopulation AFR AF= 0.0308 (1280/41592). AF 95% confidence interval is 0.0294. There are 19 homozygotes in gnomad4. There are 632 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 19 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT10A	NM_025216.3	c.85C>T	p.Leu29Leu	synonymous_variant	Exon 1 of 4	ENST00000258411.8	NP_079492.2
WNT10A	XM_011511930.2	c.85C>T	p.Leu29Leu	synonymous_variant	Exon 1 of 3		XP_011510232.1
WNT10A	XM_011511929.3	c.18-1081C>T		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.85C>T	p.Leu29Leu	synonymous_variant	Exon 1 of 4	1	NM_025216.3	ENSP00000258411.3

Frequencies

GnomAD3 genomes AF: 0.00880 AC: 1339 AN: 152232 Hom.: 19 Cov.: 32

Gnomad AFR AF: 0.0306

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00373

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00189 AC: 424 AN: 224910 Hom.: 7 AF XY: 0.00150 AC XY: 185 AN XY: 123088

Gnomad AFR exome AF: 0.0289

Gnomad AMR exome AF: 0.00109

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000351

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000405

Gnomad OTH exome AF: 0.00107

GnomAD4 exome AF: 0.000777 AC: 1128 AN: 1452478 Hom.: 11 Cov.: 31 AF XY: 0.000675 AC XY: 487 AN XY: 721548

Gnomad4 AFR exome AF: 0.0284

Gnomad4 AMR exome AF: 0.00123

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000473

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000217

Gnomad4 OTH exome AF: 0.00153

GnomAD4 genome AF: 0.00887 AC: 1351 AN: 152350 Hom.: 19 Cov.: 32 AF XY: 0.00848 AC XY: 632 AN XY: 74506

Gnomad4 AFR AF: 0.0308

Gnomad4 AMR AF: 0.00372

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00425

Alfa AF: 0.00426 Hom.: 10

Bravo AF: 0.00976

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

SchC6pf-Schulz-Passarge syndrome Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Odonto-onycho-dermal dysplasia Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Odonto-onycho-dermal dysplasia;C1835492:Tooth agenesis, selective, 4 Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Tooth agenesis, selective, 4 Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	13
DANN	Benign	0.96

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

LitVar

Other links and lift over

dbSNP: rs115839019; hg19: chr2-219745802;