NM_003392.7:c.141-9C>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_003392.7(WNT5A):c.141-9C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000312 in 1,570,194 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

WNT5A
NM_003392.7 intron

Scores

Splicing: ADA: 0.002325

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 2.50

Publications

0 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 -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 3-55479573-G-C is Benign according to our data. Variant chr3-55479573-G-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 160312.

BS2

High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT5A	NM_003392.7 link	c.141-9C>G		intron_variant	Intron 2 of 4	ENST00000264634.9	NP_003383.4	P41221-1A0A384N611B3KQX9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT5A	ENST00000264634.9 link	c.141-9C>G		intron_variant	Intron 2 of 4	1	NM_003392.7	ENSP00000264634.4		P41221-1

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000602

AC:

AN:

232556

AF XY:

0.0000635

show subpopulations

Gnomad AFR exome

AF:

0.0000666

Gnomad AMR exome

AF:

0.000258

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000935

Gnomad OTH exome

AF:

0.000544

GnomAD4 exome

AF:

0.0000289

AC:

AN:

1417868

Hom.:

Cov.:

AF XY:

0.0000343

AC XY:

AN XY:

699328

show subpopulations

African (AFR)

AF:

0.0000929

AC:

AN:

32310

American (AMR)

AF:

0.000290

AC:

AN:

41356

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24734

East Asian (EAS)

AF:

0.0000258

AC:

AN:

38818

South Asian (SAS)

AF:

0.0000504

AC:

AN:

79382

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52562

Middle Eastern (MID)

AF:

0.000179

AC:

AN:

5586

European-Non Finnish (NFE)

AF:

0.0000157

AC:

AN:

1084766

Other (OTH)

AF:

0.0000514

AC:

AN:

58354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000525

AC:

AN:

152326

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41574

American (AMR)

AF:

0.000131

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68042

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000453

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Autosomal dominant Robinow syndrome 1

Uncertain:1

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Oct 24, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

WNT5A-related disorder

Benign:1

Feb 24, 2020

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

(source)

DANN

Benign

0.72

PhyloP100

2.5

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0023

dbscSNV1_RF

Benign

0.040

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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