Genetic Variant NM_024494.3:c.63G>T (chr1-112509325-G-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_024494.3(WNT2B):c.63G>T(p.Pro21Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000699 in 1,430,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

WNT2B
NM_024494.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.32

Publications

0 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 Gene-Disease associations (from GenCC):

diarrhea 9
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

WNT2B links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 1-112509325-G-T is Benign according to our data. Variant chr1-112509325-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3680276.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.32 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024494.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WNT2B	NM_024494.3	MANE Select	c.63G>T	p.Pro21Pro	synonymous	Exon 1 of 5	NP_078613.1	Q93097-1
WNT2B	NM_004185.4		c.126-5549G>T		intron	N/A	NP_004176.2	Q93097-2
WNT2B	NM_001291880.1		c.-94-5549G>T		intron	N/A	NP_001278809.1	Q93097

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WNT2B	ENST00000369684.5	TSL:1 MANE Select	c.63G>T	p.Pro21Pro	synonymous	Exon 1 of 5	ENSP00000358698.4	Q93097-1
WNT2B	ENST00000369686.9	TSL:1	c.126-5549G>T		intron	N/A	ENSP00000358700.4	Q93097-2
WNT2B	ENST00000870348.1		c.63G>T	p.Pro21Pro	synonymous	Exon 1 of 5	ENSP00000540407.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.99e-7

AC:

AN:

1430634

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

711020

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31610

American (AMR)

AF:

0.00

AC:

AN:

41726

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25492

East Asian (EAS)

AF:

0.00

AC:

AN:

38210

South Asian (SAS)

AF:

0.00

AC:

AN:

84060

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43000

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4118

European-Non Finnish (NFE)

AF:

9.06e-7

AC:

AN:

1103156

Other (OTH)

AF:

0.00

AC:

AN:

59262

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.73

(source)

DANN

Benign

0.78

PhyloP100

-2.3

PromoterAI

-0.043

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over