Genetic Variant WNT5A:c.-413-524_-413-523insG (chr3-55487921-T-TC) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The ENST00000474267.5(WNT5A):c.-413-524_-413-523insG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0453 in 145,290 control chromosomes in the GnomAD database, including 159 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.045 ( 159 hom., cov: 32)

Exomes 𝑓: 0.036 ( 0 hom. )

Consequence

WNT5A
ENST00000474267.5 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.242

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:

WNT5A-AS1 (HGNC:40616): (WNT5A antisense RNA 1)

WNT5A-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 3-55487921-T-TC is Benign according to our data. Variant chr3-55487921-T-TC is described in ClinVar as [Benign]. Clinvar id is 1262259.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
WNT5A	XM_017007127.2 link	c.48+1010dupG	intron_variant	Intron 1 of 4	XP_016862616.1
WNT5A	XM_011534086.3 link	c.-40+2108dupG	intron_variant	Intron 6 of 9	XP_011532388.1	P41221-2A0A024R316
WNT5A	XM_017007128.2 link	c.-40+2108dupG	intron_variant	Intron 6 of 9	XP_016862617.1	P41221-2A0A024R316

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT5A	ENST00000474267.5 link	c.-413-524_-413-523insG		intron_variant	Intron 1 of 5	5		ENSP00000417310.1		P41221-1
WNT5A-AS1	ENST00000469484.1 link	n.181+42_181+43insC		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.0453

AC:

6578

AN:

145082

Hom.:

158

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0554

Gnomad AMI

AF:

0.00447

Gnomad AMR

AF:

0.0210

Gnomad ASJ

AF:

0.0469

Gnomad EAS

AF:

0.0131

Gnomad SAS

AF:

0.0689

Gnomad FIN

AF:

0.0682

Gnomad MID

AF:

0.0467

Gnomad NFE

AF:

0.0426

Gnomad OTH

AF:

0.0467

GnomAD4 exome

AF:

0.0357

AC:

AN:

140

Hom.:

Cov.:

AF XY:

0.0263

AC XY:

AN XY:

114

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 NFE exome

AF:

0.0417

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0453

AC:

6582

AN:

145150

Hom.:

159

Cov.:

AF XY:

0.0452

AC XY:

3188

AN XY:

70532

show subpopulations

Gnomad4 AFR

AF:

0.0555

Gnomad4 AMR

AF:

0.0210

Gnomad4 ASJ

AF:

0.0469

Gnomad4 EAS

AF:

0.0132

Gnomad4 SAS

AF:

0.0685

Gnomad4 FIN

AF:

0.0682

Gnomad4 NFE

AF:

0.0425

Gnomad4 OTH

AF:

0.0464

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Sep 11, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over