Genetic Variant NM_024494.3:c.*640C>T (chr1-112521149-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_024494.3(WNT2B):c.*640C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,868 control chromosomes in the GnomAD database, including 3,326 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 0.19 ( 3304 hom., cov: 31)

Exomes 𝑓: 0.20 ( 22 hom. )

Consequence

WNT2B
NM_024494.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.497

Publications

28 publications found

Variant links:

Genes affected

WNT2B (HGNC:12781): (Wnt family member 2B) This gene encodes a member of the wingless-type MMTV integration site (WNT) family of highly conserved, secreted signaling factors. WNT family members function in a variety of developmental processes including regulation of cell growth and differentiation and are characterized by a WNT-core domain. This gene may play a role in human development as well as carcinogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

WNT2B links:

ST7L (HGNC:18441): (suppression of tumorigenicity 7 like) This gene was identified by its similarity to the ST7 tumor suppressor gene found in the chromosome 7q31 region. This gene is clustered in a tail-to-tail manner with the WNT2B gene in a chromosomal region known to be deleted and rearranged in a variety of cancers. Several transcript variants encoding many different isoforms have been described, but some have not been fully characterized. [provided by RefSeq, Feb 2011]

ST7L 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=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT2B	NM_024494.3 link	c.*640C>T		3_prime_UTR_variant	Exon 5 of 5	ENST00000369684.5	NP_078613.1	Q93097-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
WNT2B	ENST00000369684.5 link	c.*640C>T	3_prime_UTR_variant	Exon 5 of 5	1	NM_024494.3	ENSP00000358698.4	Q93097-1
WNT2B	ENST00000369686.9 link	c.*640C>T	3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000358700.4	Q93097-2
WNT2B	ENST00000256640.9 link	c.*640C>T	3_prime_UTR_variant	Exon 5 of 5	2		ENSP00000256640.5	Q5TEH8

Frequencies

GnomAD3 genomes

AF:

0.186

AC:

28293

AN:

151854

Hom.:

3302

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0762

Gnomad AMI

AF:

0.294

Gnomad AMR

AF:

0.253

Gnomad ASJ

AF:

0.258

Gnomad EAS

AF:

0.458

Gnomad SAS

AF:

0.209

Gnomad FIN

AF:

0.296

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.194

Gnomad OTH

AF:

0.184

GnomAD4 exome

AF:

0.201

AC:

180

AN:

896

Hom.:

Cov.:

AF XY:

0.210

AC XY:

AN XY:

448

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.309

AC:

AN:

162

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.306

AC:

AN:

European-Finnish (FIN)

AF:

0.167

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.173

AC:

115

AN:

666

Other (OTH)

AF:

0.136

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

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:

0.186

AC:

28297

AN:

151972

Hom.:

3304

Cov.:

AF XY:

0.195

AC XY:

14473

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.0761

AC:

3157

AN:

41486

American (AMR)

AF:

0.254

AC:

3871

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.258

AC:

892

AN:

3464

East Asian (EAS)

AF:

0.458

AC:

2359

AN:

5148

South Asian (SAS)

AF:

0.209

AC:

1006

AN:

4822

European-Finnish (FIN)

AF:

0.296

AC:

3116

AN:

10532

Middle Eastern (MID)

AF:

0.129

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.194

AC:

13206

AN:

67954

Other (OTH)

AF:

0.182

AC:

385

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1096

2192

3288

4384

5480

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

302

604

906

1208

1510

<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:

0.184

Hom.:

5071

Bravo

AF:

0.184

Asia WGS

AF:

0.312

AC:

1081

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.39

(source)

DANN

Benign

0.36

PhyloP100

-0.50

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over