chr2-218882252-CGG-GGA

Variant names:

• chr2-218882252-CGG-GGA
• NM_025216.3:c.205_207delCGGinsGGA
• WNT10A p.Arg69Gly

GermlineCancer (beta)

Variant summary

Our verdict is Uncertain significance.

+2 Uncertain · Warm

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received 2 classification points (ACMG Germline Pathogenicity v2019). PM2

The NM_025216.3(WNT10A):c.205_207delCGGinsGGA (p.Arg69Gly) variant causes a missense change. Note: allele frequency estimates from gnomAD may be inaccurate for this variant type (MNP or indel longer than 3 bp) due to technology limitations. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Other variants at the same amino acid position have been reported in ClinVar (not pathogenic): p.R69Q: Uncertain_significance (ClinVar VariationId 3251508, 1 star); p.R69W: Uncertain_significance (ClinVar VariationId 582506, 1 star)

• Frequency: Genomes: not found (cov: 32)
• Consequence: WNT10A NM_025216.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.27
• 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, AD, AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, PanelApp Australia, Natera, 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

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 2 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	PM2Absent/extremely low in population databases		Absent from gnomAD (AD/XL gene) — PM2; Absent from gnomAD at well-covered site (MOI: AD+AR) (base 0.0001, raised to 0.0005 by highest known P/LP ClinVar AF 0.00141) — PM2 moderate.

Variant Effect in Transcripts

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

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	WNT10A NM_025216.3	MANE Select	c.205_207delCGGinsGGA p.Arg69Gly	missense	N/A	Prot: NP_079492.2

WNT10A NM_025216.3

MANE Select

HGVSc / HGVSpc.205_207delCGGinsGGAp.Arg69Gly

Exon rankN/A

missense

Prot: NP_079492.2

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	WNT10A ENST00000258411.8	TSL:1MANE Select	c.205_207delCGGinsGGA p.Arg69Gly	missense	N/A	Prot: ENSP00000258411.3 UniProt:
	WNT10A ENST00000964557.1		c.205_207delCGGinsGGA p.Arg69Gly	missense	N/A	Prot: ENSP00000634616.1 UniProt:
	WNT10A ENST00000865256.1		c.205_207delCGGinsGGA p.Arg69Gly	missense	N/A	Prot: ENSP00000535315.1 UniProt:

WNT10A ENST00000258411.8

TSL:1MANE Select

HGVSc / HGVSpc.205_207delCGGinsGGAp.Arg69Gly

Exon rankN/A

missense

Prot: ENSP00000258411.3UniProt: Q9GZT5

WNT10A ENST00000964557.1

HGVSc / HGVSpc.205_207delCGGinsGGAp.Arg69Gly

Exon rankN/A

missense

Prot: ENSP00000634616.1UniProt: A0ACI8VE80

WNT10A ENST00000865256.1

HGVSc / HGVSpc.205_207delCGGinsGGAp.Arg69Gly

Exon rankN/A

missense

Prot: ENSP00000535315.1UniProt: A0ACI8QEH2

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 2 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:32
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:32

Showing 2 sources

Tested, but no data found:GnomAD4 exomeIf GnomAD4 is missing, the position is probably not covered by the project.

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
PhyloP100	Benign	2.3

Showing 1 of 1 scores

Splicing Scores

No splicing scores have been computed for this variant.

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

hg19: chr2-219746974;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar