Genetic Variant NM_025216.3:c.757-1113C>T (chr2-218891661-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.773

Publications

49 publications found

Variant links:

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

WNT10A links:

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ACMG classification

Classification was made for transcript

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	Effect	Exon rank	MANE	Protein	UniProt
WNT10A	NM_025216.3 link	c.757-1113C>T	intron_variant	Intron 3 of 3	ENST00000258411.8	NP_079492.2	Q9GZT5A0A2K8FR47
WNT10A	XM_011511929.3 link	c.661-1113C>T	intron_variant	Intron 4 of 4		XP_011510231.1
WNT10A	XM_011511930.2 link	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 link	c.757-1113C>T		intron_variant	Intron 3 of 3	1	NM_025216.3	ENSP00000258411.3		Q9GZT5
WNT10A	ENST00000458582.1 link	c.263-1113C>T		intron_variant	Intron 1 of 1	3		ENSP00000388812.1		H7BZB8

Frequencies

GnomAD3 genomes

AF:

0.127

AC:

19315

AN:

152060

Hom.:

1314

Cov.:

show subpopulations

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.:

AF XY:

0.127

AC XY:

9455

AN XY:

74384

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.136

AC:

9242

AN:

68002

Other (OTH)

AF:

0.142

AC:

300

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

866

1732

2599

3465

4331

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

232

464

696

928

1160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.86

PhyloP100

0.77

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over