Variant rs762481849 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003392.7(WNT5A):c.1116G>C(p.Glu372Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

WNT5A
NM_003392.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.59

Variant links:

Genes affected

WNT5A (HGNC:12784): (Wnt family member 5A) The WNT gene family consists of structurally related genes which 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 encodes a member of the WNT family that signals through both the canonical and non-canonical WNT pathways. This protein is a ligand for the seven transmembrane receptor frizzled-5 and the tyrosine kinase orphan receptor 2. This protein plays an essential role in regulating developmental pathways during embryogenesis. This protein may also play a role in oncogenesis. Mutations in this gene are the cause of autosomal dominant Robinow syndrome. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2012]

WNT5A links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25125712).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT5A	NM_003392.7 link	c.1116G>C	p.Glu372Asp	missense_variant	Exon 5 of 5	ENST00000264634.9	NP_003383.4	P41221-1A0A384N611B3KQX9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
WNT5A	ENST00000264634.9 link	c.1116G>C	p.Glu372Asp	missense_variant	Exon 5 of 5	1	NM_003392.7	ENSP00000264634.4	P41221-1
WNT5A	ENST00000474267.5 link	c.1116G>C	p.Glu372Asp	missense_variant	Exon 6 of 6	5		ENSP00000417310.1	P41221-1
WNT5A	ENST00000497027.5 link	c.1071G>C	p.Glu357Asp	missense_variant	Exon 5 of 5	2		ENSP00000420104.1	P41221-2
WNT5A	ENST00000493406.1 link	n.23G>C		non_coding_transcript_exon_variant	Exon 1 of 2	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

250958

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135676

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461744

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727168

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.000111

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Uncertain

0.052

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.71

D;D;.

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.59

.;T;T

M_CAP

Benign

0.025

MetaRNN

Benign

0.25

T;T;T

MetaSVM

Benign

-0.45

MutationAssessor

Benign

1.8

L;L;.

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.4

N;N;N

REVEL

Benign

0.28

Sift

Benign

0.16

T;T;T

Sift4G

Benign

0.24

T;T;T

Polyphen

0.86

P;P;.

Vest4

0.30

MutPred

0.45

Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);.;

MVP

0.35

MPC

0.96

ClinPred

0.63

GERP RS

3.9

Varity_R

0.22

gMVP

0.20

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over