Genetic Variant NM_024494.3:c.1170A>G (chr1-112520503-A-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_024494.3(WNT2B):c.1170A>G(p.Gln390Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 1,612,766 control chromosomes in the GnomAD database, including 177,367 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 18157 hom., cov: 31)

Exomes 𝑓: 0.46 ( 159210 hom. )

Consequence

WNT2B
NM_024494.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.46

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 1-112520503-A-G is Benign according to our data. Variant chr1-112520503-A-G is described in ClinVar as [Benign]. Clinvar id is 1608306.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.46 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT2B	NM_024494.3 link	c.1170A>G	p.Gln390Gln	synonymous_variant	Exon 5 of 5	ENST00000369684.5	NP_078613.1	Q93097-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
WNT2B	ENST00000369684.5 link	c.1170A>G	p.Gln390Gln	synonymous_variant	Exon 5 of 5	1	NM_024494.3	ENSP00000358698.4	Q93097-1
WNT2B	ENST00000369686.9 link	c.1113A>G	p.Gln371Gln	synonymous_variant	Exon 6 of 6	1		ENSP00000358700.4	Q93097-2
WNT2B	ENST00000256640.9 link	c.894A>G	p.Gln298Gln	synonymous_variant	Exon 5 of 5	2		ENSP00000256640.5	Q5TEH8

Frequencies

GnomAD3 genomes

AF:

0.484

AC:

73529

AN:

151800

Hom.:

18135

Cov.:

show subpopulations

Gnomad AFR

AF:

0.536

Gnomad AMI

AF:

0.533

Gnomad AMR

AF:

0.444

Gnomad ASJ

AF:

0.484

Gnomad EAS

AF:

0.642

Gnomad SAS

AF:

0.334

Gnomad FIN

AF:

0.501

Gnomad MID

AF:

0.401

Gnomad NFE

AF:

0.459

Gnomad OTH

AF:

0.446

GnomAD3 exomes

AF:

0.473

AC:

117938

AN:

249518

Hom.:

28303

AF XY:

0.463

AC XY:

62497

AN XY:

134842

show subpopulations

Gnomad AFR exome

AF:

0.529

Gnomad AMR exome

AF:

0.486

Gnomad ASJ exome

AF:

0.487

Gnomad EAS exome

AF:

0.648

Gnomad SAS exome

AF:

0.339

Gnomad FIN exome

AF:

0.498

Gnomad NFE exome

AF:

0.462

Gnomad OTH exome

AF:

0.464

GnomAD4 exome

AF:

0.464

AC:

678397

AN:

1460848

Hom.:

159210

Cov.:

AF XY:

0.459

AC XY:

333912

AN XY:

726698

show subpopulations

Gnomad4 AFR exome

AF:

0.532

Gnomad4 AMR exome

AF:

0.487

Gnomad4 ASJ exome

AF:

0.482

Gnomad4 EAS exome

AF:

0.638

Gnomad4 SAS exome

AF:

0.342

Gnomad4 FIN exome

AF:

0.501

Gnomad4 NFE exome

AF:

0.463

Gnomad4 OTH exome

AF:

0.465

GnomAD4 genome

AF:

0.484

AC:

73582

AN:

151918

Hom.:

18157

Cov.:

AF XY:

0.485

AC XY:

35972

AN XY:

74238

show subpopulations

Gnomad4 AFR

AF:

0.536

Gnomad4 AMR

AF:

0.444

Gnomad4 ASJ

AF:

0.484

Gnomad4 EAS

AF:

0.642

Gnomad4 SAS

AF:

0.333

Gnomad4 FIN

AF:

0.501

Gnomad4 NFE

AF:

0.459

Gnomad4 OTH

AF:

0.443

Alfa

AF:

0.474

Hom.:

12694

Bravo

AF:

0.485

Asia WGS

AF:

0.467

AC:

1624

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

7.5

DANN

Benign

0.73

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over