Genetic Variant WNT5A:c.*1952_*1953dupTT (chr3-55468138-T-TAA) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6BA1

The NM_003392.7(WNT5A):c.*1952_*1953dupTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.043 ( 352 hom., cov: 0)

Failed GnomAD Quality Control

Consequence

WNT5A
NM_003392.7 3_prime_UTR

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: -0.0260

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: G2P, Labcorp Genetics (formerly Invitae), Illumina, Ambry Genetics
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.

BP6

Variant 3-55468138-T-TAA is Benign according to our data. Variant chr3-55468138-T-TAA is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 346240.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003392.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
WNT5A	NM_003392.7	MANE Select	c.1952_1953dupTT	3_prime_UTR	Exon 5 of 5	NP_003383.4
WNT5A	NM_001256105.1		c.1952_1953dupTT	3_prime_UTR	Exon 5 of 5	NP_001243034.1	P41221-2
WNT5A	NM_001377271.1		c.1952_1953dupTT	3_prime_UTR	Exon 5 of 5	NP_001364200.1	P41221-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT5A	ENST00000264634.9	TSL:1 MANE Select	c.1952_1953dupTT		3_prime_UTR	Exon 5 of 5	ENSP00000264634.4	P41221-1
	WNT5A	ENST00000474267.5	TSL:5	c.1952_1953dupTT		3_prime_UTR	Exon 6 of 6	ENSP00000417310.1	P41221-1

Frequencies

GnomAD3 genomes

AF:

0.0429

AC:

5749

AN:

133892

Hom.:

353

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0118

Gnomad AMI

AF:

0.0276

Gnomad AMR

AF:

0.180

Gnomad ASJ

AF:

0.0389

Gnomad EAS

AF:

0.0610

Gnomad SAS

AF:

0.0214

Gnomad FIN

AF:

0.0138

Gnomad MID

AF:

0.0180

Gnomad NFE

AF:

0.0357

Gnomad OTH

AF:

0.0503

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.0430

AC:

5753

AN:

133900

Hom.:

352

Cov.:

AF XY:

0.0447

AC XY:

2847

AN XY:

63648

show subpopulations

African (AFR)

AF:

0.0118

AC:

433

AN:

36828

American (AMR)

AF:

0.180

AC:

2369

AN:

13134

Ashkenazi Jewish (ASJ)

AF:

0.0389

AC:

128

AN:

3288

East Asian (EAS)

AF:

0.0611

AC:

281

AN:

4596

South Asian (SAS)

AF:

0.0215

AC:

AN:

4092

European-Finnish (FIN)

AF:

0.0138

AC:

AN:

5934

Middle Eastern (MID)

AF:

0.0198

AC:

AN:

252

European-Non Finnish (NFE)

AF:

0.0357

AC:

2252

AN:

63090

Other (OTH)

AF:

0.0501

AC:

AN:

1818

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

215

430

646

861

1076

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

186

248

310

<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.:

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Autosomal dominant Robinow syndrome 1 (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.026

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

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3-55468138-TAAAAAAA-TAAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over