17-46872524-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2 BP4_Strong BP6_Very_Strong

The NM_003396.3(WNT9B):c.85G>A(p.Gly29Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000195 in 1,538,606 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00079 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: WNT9B NM_003396.3 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 6.58

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 -10 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.021863729).
• BP6: Variant 17-46872524-G-A is Benign according to our data. Variant chr17-46872524-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2647871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WNT9B	NM_003396.3	c.85G>A	p.Gly29Arg	missense_variant	2/4	ENST00000290015.7
WNT9B	NM_001320458.2	c.85G>A	p.Gly29Arg	missense_variant	2/5
WNT9B	XM_011525178.3	c.103G>A	p.Gly35Arg	missense_variant	2/4
LRRC37A2	XM_024450773.2	c.4810-176532G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNT9B	ENST00000290015.7	c.85G>A	p.Gly29Arg	missense_variant	2/4	1	NM_003396.3	P1
WNT9B	ENST00000393461.2	c.85G>A	p.Gly29Arg	missense_variant	2/5	2
WNT9B	ENST00000575372.5	c.103G>A	p.Gly35Arg	missense_variant	2/3	4

Frequencies

GnomAD3 genomes AF: 0.000802 AC: 122 AN: 152184 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.000377 AC: 73 AN: 193530 Hom.: 0 AF XY: 0.000291 AC XY: 30 AN XY: 103146

Gnomad AFR exome AF: 0.00286

Gnomad AMR exome AF: 0.000493

Gnomad ASJ exome AF: 0.00119

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000532

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000783

Gnomad OTH exome AF: 0.000884

GnomAD4 exome AF: 0.000129 AC: 179 AN: 1386304 Hom.: 0 Cov.: 31 AF XY: 0.000129 AC XY: 88 AN XY: 681096

Gnomad4 AFR exome AF: 0.00293

Gnomad4 AMR exome AF: 0.000467

Gnomad4 ASJ exome AF: 0.00126

Gnomad4 EAS exome AF: 0.0000261

Gnomad4 SAS exome AF: 0.0000135

Gnomad4 FIN exome AF: 0.0000198

Gnomad4 NFE exome AF: 0.0000205

Gnomad4 OTH exome AF: 0.000298

GnomAD4 genome AF: 0.000794 AC: 121 AN: 152302 Hom.: 1 Cov.: 32 AF XY: 0.000873 AC XY: 65 AN XY: 74470

Gnomad4 AFR AF: 0.00262

Gnomad4 AMR AF: 0.000261

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.000217 Hom.: 0

Bravo AF: 0.000956

ESP6500AA AF: 0.00227 AC: 10

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000381 AC: 46

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Invitae	Oct 29, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2022	WNT9B: PP3, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Benign	-0.044	T
BayesDel_noAF	Pathogenic	0.16
Cadd	Pathogenic	29
Dann	Pathogenic	1.0
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.022	T;T;T
MetaSVM	Uncertain	-0.0040	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.95	D
Sift4G	Uncertain	0.021	D;D;D
Polyphen		1.0, 1.0	.;D;D
Vest4		0.88, 0.90
MutPred		0.48		.;Loss of methylation at R30 (P = 0.0268);Loss of methylation at R30 (P = 0.0268);
MVP		0.93
MPC		0.99
ClinPred		0.039	T
GERP RS		4.6
Varity_R		0.47
gMVP		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs147055144; hg19: chr17-44949890;