Variant 17-46851643-G-GC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5

The NM_003396.3(WNT9B):c.11dup(p.Pro5AlafsTer52) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,275,602 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (no stars).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

WNT9B
NM_003396.3 frameshift

Scores

Not classified

Clinical Significance

Likely pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 2.44

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:):

LRRC37A2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 17-46851643-G-GC is Pathogenic according to our data. Variant chr17-46851643-G-GC is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1344867.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
WNT9B	NM_003396.3 linkuse as main transcript	c.11dup	p.Pro5AlafsTer52	frameshift_variant	1/4	ENST00000290015.7
WNT9B	NM_001320458.2 linkuse as main transcript	c.11dup	p.Pro5AlafsTer52	frameshift_variant	1/5
WNT9B	XM_011525178.3 linkuse as main transcript	c.95+18209dup		intron_variant
LRRC37A2	XM_024450773.2 linkuse as main transcript	c.4810-197407dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
WNT9B	ENST00000290015.7 linkuse as main transcript	c.11dup	p.Pro5AlafsTer52	frameshift_variant	1/4	1	NM_003396.3	P1
WNT9B	ENST00000393461.2 linkuse as main transcript	c.11dup	p.Pro5AlafsTer52	frameshift_variant	1/5	2
WNT9B	ENST00000575372.5 linkuse as main transcript	c.95+18209dup		intron_variant		4

Frequencies

GnomAD3 genomes

AF:

0.0000264

AC:

AN:

151500

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000288

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000133

AC:

AN:

1124102

Hom.:

Cov.:

AF XY:

0.0000166

AC XY:

AN XY:

542458

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000183

Gnomad4 FIN exome

AF:

0.000168

Gnomad4 NFE exome

AF:

0.00000527

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000264

AC:

AN:

151500

Hom.:

Cov.:

AF XY:

0.0000406

AC XY:

AN XY:

73970

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000288

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Renal hypoplasia;C1561643:Chronic kidney disease;C3536714:Renal dysplasia

Pathogenic:1

Likely pathogenic, no assertion criteria provided

literature only

Yale Center for Mendelian Genomics, Yale University

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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