rs2385199

Variant names:

• chr2-218886024-A-G
• rs2385199
• NM_025216.3:c.376+3601A>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.376+3601A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 152,082 control chromosomes in the GnomAD database, including 5,479 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 0.25 (5479 hom., cov: 32)
• Consequence: WNT10A NM_025216.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.436
• Publications: 12 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=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.389 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.376+3601A>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.376+3601A>G		intron	N/A	ENSP00000258411.3
	WNT10A	ENST00000458582.1	TSL:3	c.262+3601A>G		intron	N/A	ENSP00000388812.1
	WNT10A	ENST00000483911.1	TSL:3	n.474+1701A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38097 AN: 151964 Hom.: 5467 Cov.: 32

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.251 AC: 38142 AN: 152082 Hom.: 5479 Cov.: 32 AF XY: 0.249 AC XY: 18530 AN XY: 74360

African (AFR) AF: 0.394 AC: 16324 AN: 41438

American (AMR) AF: 0.220 AC: 3371 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 542 AN: 3472

East Asian (EAS) AF: 0.253 AC: 1307 AN: 5172

South Asian (SAS) AF: 0.303 AC: 1462 AN: 4822

European-Finnish (FIN) AF: 0.172 AC: 1824 AN: 10584

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12592 AN: 67988

Other (OTH) AF: 0.244 AC: 515 AN: 2110

Alfa AF: 0.200 Hom.: 3823

Bravo AF: 0.258

Asia WGS AF: 0.325 AC: 1126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.6
DANN	Benign	0.85
PhyloP100		-0.44
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: rs2385199; hg19: chr2-219750746;