17-46872720-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 5.78

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]

LRRC37A2 (HGNC:):

ACMG classification

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 GnomAd at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WNT9B	NM_003396.3	c.281G>A	p.Arg94Gln	missense_variant	2/4	ENST00000290015.7
WNT9B	NM_001320458.2	c.281G>A	p.Arg94Gln	missense_variant	2/5
WNT9B	XM_011525178.3	c.299G>A	p.Arg100Gln	missense_variant	2/4
LRRC37A2	XM_024450773.2	c.4810-176336G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNT9B	ENST00000290015.7	c.281G>A	p.Arg94Gln	missense_variant	2/4	1	NM_003396.3	P1
WNT9B	ENST00000393461.2	c.281G>A	p.Arg94Gln	missense_variant	2/5	2
WNT9B	ENST00000575372.5	c.299G>A	p.Arg100Gln	missense_variant	2/3	4

Frequencies

GnomAD3 genomes AF: 0.00458 AC: 696 AN: 152056 Hom.: 8 Cov.: 32

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.: 4 AF XY: 0.000968 AC XY: 130 AN XY: 134254

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.: 7 Cov.: 32 AF XY: 0.000461 AC XY: 335 AN XY: 726714

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.: 8 Cov.: 32 AF XY: 0.00441 AC XY: 328 AN XY: 74400

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.: 0

Bravo AF: 0.00530

ESP6500AA AF: 0.0132 AC: 58

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00147 AC: 178

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

WNT9B-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 16, 2019

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). -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 24, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.31
Cadd	Benign	21
Dann	Uncertain	1.0
Eigen	Benign	-0.071
Eigen_PC	Benign	0.023
FATHMM_MKL	Pathogenic	0.98	D
MetaRNN	Benign	0.0090	T;T;T
MetaSVM	Benign	-0.65	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.51	T
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	T
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

Other links and lift over

dbSNP: rs75199851; hg19: chr17-44950086;