17-46872720-G-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_003396.3(WNT9B):c.281G>A(p.Arg94Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00088 in 1,613,098 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0046 ( 8 hom., cov: 32)

Exomes 𝑓: 0.00050 ( 7 hom. )

Consequence

WNT9B
NM_003396.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 5.78

Variant links:

Genes affected

WNT9B (HGNC:12779): (Wnt family member 9B) The WNT gene family consists of structurally related genes that 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. This gene is a member of the WNT gene family. Study of its expression in the teratocarcinoma cell line NT2 suggests that it may be implicated in the early process of neuronal differentiation of NT2 cells induced by retinoic acid. This gene is clustered with WNT3, another family member, in the chromosome 17q21 region. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

WNT9B links:

LRRC37A2 (HGNC:32404): (leucine rich repeat containing 37 member A2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LRRC37A2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00896439).

BP6

Variant 17-46872720-G-A is Benign according to our data. Variant chr17-46872720-G-A is described in ClinVar as [Benign]. Clinvar id is 1623374.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT9B	NM_003396.3 link	c.281G>A	p.Arg94Gln	missense_variant	Exon 2 of 4	ENST00000290015.7	NP_003387.1	O14905
WNT9B	NM_001320458.2 link	c.281G>A	p.Arg94Gln	missense_variant	Exon 2 of 5		NP_001307387.1	E7EPC3
WNT9B	XM_011525178.3 link	c.299G>A	p.Arg100Gln	missense_variant	Exon 2 of 4		XP_011523480.1
LRRC37A2	XM_024450773.2 link	c.4810-176336G>A		intron_variant	Intron 10 of 10		XP_024306541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
WNT9B	ENST00000290015.7 link	c.281G>A	p.Arg94Gln	missense_variant	Exon 2 of 4	1	NM_003396.3	ENSP00000290015.2	O14905
WNT9B	ENST00000393461.2 link	c.281G>A	p.Arg94Gln	missense_variant	Exon 2 of 5	2		ENSP00000377105.2	E7EPC3
WNT9B	ENST00000575372.5 link	c.299G>A	p.Arg100Gln	missense_variant	Exon 2 of 3	4		ENSP00000458192.1	I3L0L8

Frequencies

GnomAD3 genomes

AF:

0.00458

AC:

696

AN:

152056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0160

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00115

AC:

285

AN:

246984

Hom.:

AF XY:

0.000968

AC XY:

130

AN XY:

134254

show subpopulations

Gnomad AFR exome

AF:

0.0152

Gnomad AMR exome

AF:

0.000900

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000982

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000724

Gnomad OTH exome

AF:

0.000496

GnomAD4 exome

AF:

0.000496

AC:

725

AN:

1460924

Hom.:

Cov.:

AF XY:

0.000461

AC XY:

335

AN XY:

726714

show subpopulations

Gnomad4 AFR exome

AF:

0.0158

Gnomad4 AMR exome

AF:

0.00130

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000387

Gnomad4 OTH exome

AF:

0.00136

GnomAD4 genome

AF:

0.00457

AC:

695

AN:

152174

Hom.:

Cov.:

AF XY:

0.00441

AC XY:

328

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.0160

Gnomad4 AMR

AF:

0.00164

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00105

Hom.:

Bravo

AF:

0.00530

ESP6500AA

AF:

0.0132

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00147

AC:

178

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 13, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

WNT9B-related disorder

Benign:1

Jul 16, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.74

.;D;.

Eigen

Benign

-0.071

Eigen_PC

Benign

0.023

FATHMM_MKL

Pathogenic

0.98

MetaRNN

Benign

0.0090

T;T;T

MetaSVM

Benign

-0.65

MutationAssessor

Uncertain

2.4

.;M;.

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-2.7

.;D;D

REVEL

Uncertain

0.36

Sift

Benign

0.12

.;T;D

Sift4G

Uncertain

0.0080

D;D;D

Polyphen

0.016, 0.31

.;B;B

Vest4

0.41, 0.40

MVP

0.80

MPC

0.35

ClinPred

0.028

GERP RS

3.5

Varity_R

0.25

gMVP

0.74

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