Genetic Variant WNT5A:c.*1950_*1953dupTTTT (chr3-55468138-T-TAAAA) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_003392.7(WNT5A):c.*1950_*1953dupTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.066 ( 398 hom., cov: 0)

Failed GnomAD Quality Control

Consequence

WNT5A
NM_003392.7 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B: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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 3-55468138-T-TAAAA is Benign according to our data. Variant chr3-55468138-T-TAAAA is described in ClinVar as Benign. ClinVar VariationId is 1242175.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0938 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.1950_1953dupTTTT	3_prime_UTR	Exon 5 of 5	NP_003383.4
WNT5A	NM_001256105.1		c.1950_1953dupTTTT	3_prime_UTR	Exon 5 of 5	NP_001243034.1	P41221-2
WNT5A	NM_001377271.1		c.1950_1953dupTTTT	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.1950_1953dupTTTT		3_prime_UTR	Exon 5 of 5	ENSP00000264634.4	P41221-1
	WNT5A	ENST00000474267.5	TSL:5	c.1950_1953dupTTTT		3_prime_UTR	Exon 6 of 6	ENSP00000417310.1	P41221-1

Frequencies

GnomAD3 genomes

AF:

0.0665

AC:

8886

AN:

133692

Hom.:

398

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0198

Gnomad AMI

AF:

0.0565

Gnomad AMR

AF:

0.0531

Gnomad ASJ

AF:

0.0825

Gnomad EAS

AF:

0.000867

Gnomad SAS

AF:

0.0651

Gnomad FIN

AF:

0.120

Gnomad MID

AF:

0.0978

Gnomad NFE

AF:

0.0958

Gnomad OTH

AF:

0.0575

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

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:

0.0664

AC:

8883

AN:

133698

Hom.:

398

Cov.:

AF XY:

0.0672

AC XY:

4269

AN XY:

63550

show subpopulations

African (AFR)

AF:

0.0198

AC:

728

AN:

36820

American (AMR)

AF:

0.0531

AC:

697

AN:

13132

Ashkenazi Jewish (ASJ)

AF:

0.0825

AC:

271

AN:

3284

East Asian (EAS)

AF:

0.000870

AC:

AN:

4600

South Asian (SAS)

AF:

0.0658

AC:

268

AN:

4074

European-Finnish (FIN)

AF:

0.120

AC:

710

AN:

5902

Middle Eastern (MID)

AF:

0.100

AC:

AN:

250

European-Non Finnish (NFE)

AF:

0.0958

AC:

6029

AN:

62952

Other (OTH)

AF:

0.0562

AC:

102

AN:

1816

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

340

679

1019

1358

1698

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

220

330

440

550

<30

30-35

35-40

40-45

45-50

50-55

55-60

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>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.026

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over