17-46851642-C-A

Position:

• chr17-46851642-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000290015.7(WNT9B):​c.4C>A​(p.Arg2Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: WNT9B ENST00000290015.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.92

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNT9B	NM_003396.3	c.4C>A	p.Arg2Ser	missense_variant	1/4	ENST00000290015.7	NP_003387.1
WNT9B	NM_001320458.2	c.4C>A	p.Arg2Ser	missense_variant	1/5		NP_001307387.1
WNT9B	XM_011525178.3	c.95+18202C>A		intron_variant			XP_011523480.1
LRRC37A2	XM_024450773.2	c.4810-197414C>A		intron_variant			XP_024306541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WNT9B	ENST00000290015.7	c.4C>A	p.Arg2Ser	missense_variant	1/4	1	NM_003396.3	ENSP00000290015	P1
WNT9B	ENST00000393461.2	c.4C>A	p.Arg2Ser	missense_variant	1/5	2		ENSP00000377105
WNT9B	ENST00000575372.5	c.95+18202C>A		intron_variant		4		ENSP00000458192

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1123050 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 541892

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 19, 2022

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with WNT9B-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 2 of the WNT9B protein (p.Arg2Ser). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T;.
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.69	D
M_CAP	Pathogenic	0.92	D
MetaRNN	Uncertain	0.43	T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	0.20	N;.
MutationTaster	Benign	0.93	N;N
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	0.090	N;N
REVEL	Benign	0.28
Sift	Benign	0.57	T;D
Sift4G	Benign	0.72	T;T
Polyphen		0.013	B;B
Vest4		0.33
MutPred		0.28		Gain of glycosylation at R2 (P = 0.0024);Gain of glycosylation at R2 (P = 0.0024);
MVP		0.84
MPC		0.29
ClinPred		0.71	D
GERP RS		3.8
Varity_R		0.22
gMVP		0.33

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-44929008;