rs147104982

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_003392.7(WNT5A):c.405G>T(p.Thr135Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0437 in 1,395,110 control chromosomes in the GnomAD database, including 1,564 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.028 ( 83 hom., cov: 28)

Exomes 𝑓: 0.046 ( 1481 hom. )

Consequence

WNT5A
NM_003392.7 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.10

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

autosomal dominant Robinow syndrome 1
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
autosomal dominant Robinow syndrome
Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, ClinGen

WNT5A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.29).

BP6

Variant 3-55474616-C-A is Benign according to our data. Variant chr3-55474616-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 160315.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.1 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT5A	NM_003392.7 link	c.405G>T	p.Thr135Thr	synonymous_variant	Exon 4 of 5	ENST00000264634.9	NP_003383.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
WNT5A	ENST00000264634.9 link	c.405G>T	p.Thr135Thr	synonymous_variant	Exon 4 of 5	1	NM_003392.7	ENSP00000264634.4
WNT5A	ENST00000474267.5 link	c.405G>T	p.Thr135Thr	synonymous_variant	Exon 5 of 6	5		ENSP00000417310.1
WNT5A	ENST00000497027.5 link	c.360G>T	p.Thr120Thr	synonymous_variant	Exon 4 of 5	2		ENSP00000420104.1
WNT5A	ENST00000482079.1 link	c.360G>T	p.Thr120Thr	synonymous_variant	Exon 3 of 3	2		ENSP00000418184.1

Frequencies

GnomAD3 genomes

AF:

0.0279

AC:

4023

AN:

144424

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00844

Gnomad AMI

AF:

0.00451

Gnomad AMR

AF:

0.0192

Gnomad ASJ

AF:

0.00817

Gnomad EAS

AF:

0.000219

Gnomad SAS

AF:

0.0234

Gnomad FIN

AF:

0.0237

Gnomad MID

AF:

0.00649

Gnomad NFE

AF:

0.0453

Gnomad OTH

AF:

0.0289

GnomAD2 exomes

AF:

0.0291

AC:

1589

AN:

54660

AF XY:

0.0298

show subpopulations

Gnomad AFR exome

AF:

0.00858

Gnomad AMR exome

AF:

0.0180

Gnomad ASJ exome

AF:

0.0141

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0236

Gnomad NFE exome

AF:

0.0481

Gnomad OTH exome

AF:

0.0323

GnomAD4 exome

AF:

0.0456

AC:

57013

AN:

1250590

Hom.:

1481

Cov.:

AF XY:

0.0447

AC XY:

27115

AN XY:

606386

show subpopulations

African (AFR)

AF:

0.00614

AC:

156

AN:

25390

American (AMR)

AF:

0.0185

AC:

348

AN:

18858

Ashkenazi Jewish (ASJ)

AF:

0.0107

AC:

185

AN:

17218

East Asian (EAS)

AF:

0.0000976

AC:

AN:

30732

South Asian (SAS)

AF:

0.0234

AC:

1436

AN:

61434

European-Finnish (FIN)

AF:

0.0261

AC:

868

AN:

33268

Middle Eastern (MID)

AF:

0.0114

AC:

AN:

3942

European-Non Finnish (NFE)

AF:

0.0515

AC:

51919

AN:

1009006

Other (OTH)

AF:

0.0405

AC:

2053

AN:

50742

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

2999

5998

8997

11996

14995

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2042

4084

6126

8168

10210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0278

AC:

4020

AN:

144520

Hom.:

Cov.:

AF XY:

0.0259

AC XY:

1818

AN XY:

70240

show subpopulations

African (AFR)

AF:

0.00842

AC:

328

AN:

38954

American (AMR)

AF:

0.0192

AC:

279

AN:

14520

Ashkenazi Jewish (ASJ)

AF:

0.00817

AC:

AN:

3428

East Asian (EAS)

AF:

0.000220

AC:

AN:

4548

South Asian (SAS)

AF:

0.0234

AC:

AN:

4196

European-Finnish (FIN)

AF:

0.0237

AC:

226

AN:

9544

Middle Eastern (MID)

AF:

0.00690

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0453

AC:

2996

AN:

66132

Other (OTH)

AF:

0.0287

AC:

AN:

2022

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.522

Heterozygous variant carriers

176

351

527

702

878

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0368

Hom.:

Bravo

AF:

0.0267

Asia WGS

AF:

0.0100

AC:

AN:

3474

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 01, 2021

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Jun 07, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.29

CADD

Benign

7.3

(source)

DANN

Benign

0.93

PhyloP100

-1.1

Mutation Taster

=85/15

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over