dbSNP rs2228946: WNT2:c.*124G>A (chr7-117278031-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_003391.3(WNT2):c.*124G>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 0.201 in 1,121,734 control chromosomes in the GnomAD database, including 24,899 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 0.23 ( 4530 hom., cov: 33)

Exomes 𝑓: 0.20 ( 20369 hom. )

Consequence

WNT2
NM_003391.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.25

Publications

12 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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new If you want to explore the variant's impact on the transcript NM_003391.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.24).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.325 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.*124G>A		3_prime_UTR	Exon 5 of 5	NP_003382.1	P09544
	WNT2	NR_024047.2		n.1212G>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.*124G>A	3_prime_UTR	Exon 5 of 5	ENSP00000265441.3	P09544
WNT2	ENST00000950642.1		c.*124G>A	3_prime_UTR	Exon 4 of 4	ENSP00000620701.1
WNT2	ENST00000449446.5	TSL:3	n.*810G>A	non_coding_transcript_exon	Exon 5 of 5	ENSP00000389643.1	F8WDR1

Frequencies

GnomAD3 genomes

AF:

0.231

AC:

35190

AN:

152018

Hom.:

4526

Cov.:

show subpopulations

Gnomad AFR

AF:

0.329

Gnomad AMI

AF:

0.365

Gnomad AMR

AF:

0.157

Gnomad ASJ

AF:

0.204

Gnomad EAS

AF:

0.0156

Gnomad SAS

AF:

0.116

Gnomad FIN

AF:

0.163

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.225

Gnomad OTH

AF:

0.203

GnomAD4 exome

AF:

0.196

AC:

190258

AN:

969598

Hom.:

20369

Cov.:

AF XY:

0.195

AC XY:

94567

AN XY:

485414

show subpopulations

African (AFR)

AF:

0.336

AC:

7569

AN:

22560

American (AMR)

AF:

0.121

AC:

3203

AN:

26540

Ashkenazi Jewish (ASJ)

AF:

0.206

AC:

3660

AN:

17774

East Asian (EAS)

AF:

0.0150

AC:

516

AN:

34334

South Asian (SAS)

AF:

0.112

AC:

6724

AN:

59852

European-Finnish (FIN)

AF:

0.176

AC:

7642

AN:

43366

Middle Eastern (MID)

AF:

0.212

AC:

977

AN:

4616

European-Non Finnish (NFE)

AF:

0.212

AC:

151704

AN:

717268

Other (OTH)

AF:

0.191

AC:

8263

AN:

43288

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

7637

15274

22912

30549

38186

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4434

8868

13302

17736

22170

<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:

0.232

AC:

35230

AN:

152136

Hom.:

4530

Cov.:

AF XY:

0.224

AC XY:

16690

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.329

AC:

13656

AN:

41492

American (AMR)

AF:

0.157

AC:

2397

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.204

AC:

709

AN:

3470

East Asian (EAS)

AF:

0.0163

AC:

AN:

5164

South Asian (SAS)

AF:

0.116

AC:

557

AN:

4822

European-Finnish (FIN)

AF:

0.163

AC:

1726

AN:

10588

Middle Eastern (MID)

AF:

0.214

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.225

AC:

15282

AN:

67984

Other (OTH)

AF:

0.200

AC:

423

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1369

2739

4108

5478

6847

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

356

712

1068

1424

1780

<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:

0.222

Hom.:

11613

Bravo

AF:

0.236

Asia WGS

AF:

0.0790

AC:

277

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Benign

0.86

PhyloP100

2.3

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

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

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