Genetic Variant WNT2:c.*1091G>A (chr7-117277064-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003391.3(WNT2):c.*1091G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 152,778 control chromosomes in the GnomAD database, including 13,235 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 0.41 ( 13169 hom., cov: 32)

Exomes 𝑓: 0.43 ( 66 hom. )

Consequence

WNT2
NM_003391.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.23

Publications

40 publications found

Variant links:

Genes affected

WNT2 (HGNC:12780): (Wnt family member 2) This gene is a member of the WNT gene family. 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. Alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, Jul 2008]

WNT2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003391.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT2	NM_003391.3	MANE Select	c.*1091G>A		3_prime_UTR	Exon 5 of 5	NP_003382.1	P09544
	WNT2	NR_024047.2		n.2179G>A		non_coding_transcript_exon	Exon 5 of 5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
WNT2	ENST00000265441.8	TSL:1 MANE Select	c.*1091G>A	3_prime_UTR	Exon 5 of 5	ENSP00000265441.3	P09544
WNT2	ENST00000647844.1		n.*2089G>A	non_coding_transcript_exon	Exon 6 of 6	ENSP00000497695.1	A0A3B3ITC9
WNT2	ENST00000647844.1		n.*2089G>A	3_prime_UTR	Exon 6 of 6	ENSP00000497695.1	A0A3B3ITC9

Frequencies

GnomAD3 genomes

AF:

0.409

AC:

62182

AN:

151928

Hom.:

13180

Cov.:

show subpopulations

Gnomad AFR

AF:

0.320

Gnomad AMI

AF:

0.512

Gnomad AMR

AF:

0.402

Gnomad ASJ

AF:

0.480

Gnomad EAS

AF:

0.225

Gnomad SAS

AF:

0.295

Gnomad FIN

AF:

0.511

Gnomad MID

AF:

0.538

Gnomad NFE

AF:

0.465

Gnomad OTH

AF:

0.437

GnomAD4 exome

AF:

0.426

AC:

311

AN:

730

Hom.:

Cov.:

AF XY:

0.459

AC XY:

179

AN XY:

390

show subpopulations

African (AFR)

AF:

0.300

AC:

AN:

American (AMR)

AF:

0.625

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.458

AC:

AN:

East Asian (EAS)

AF:

0.183

AC:

AN:

104

South Asian (SAS)

AF:

0.750

AC:

AN:

European-Finnish (FIN)

AF:

0.588

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.452

AC:

206

AN:

456

Other (OTH)

AF:

0.477

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.409

AC:

62172

AN:

152048

Hom.:

13169

Cov.:

AF XY:

0.409

AC XY:

30354

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.320

AC:

13254

AN:

41462

American (AMR)

AF:

0.401

AC:

6129

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.480

AC:

1666

AN:

3468

East Asian (EAS)

AF:

0.225

AC:

1163

AN:

5164

South Asian (SAS)

AF:

0.295

AC:

1423

AN:

4818

European-Finnish (FIN)

AF:

0.511

AC:

5397

AN:

10558

Middle Eastern (MID)

AF:

0.527

AC:

154

AN:

292

European-Non Finnish (NFE)

AF:

0.465

AC:

31603

AN:

67966

Other (OTH)

AF:

0.433

AC:

916

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1867

3733

5600

7466

9333

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

592

1184

1776

2368

2960

<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:

0.440

Hom.:

61924

Bravo

AF:

0.398

Asia WGS

AF:

0.255

AC:

888

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.14

(source)

DANN

Benign

0.71

PhyloP100

-2.2

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over