3-55468223-G-A

Position:

• chr3-55468223-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003392.7(WNT5A):​c.*1869C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0751 in 151,286 control chromosomes in the GnomAD database, including 738 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.075 (738 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: WNT5A NM_003392.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.584

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 3-55468223-G-A is Benign according to our data. Variant chr3-55468223-G-A is described in ClinVar as [Benign]. Clinvar id is 1252563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNT5A	NM_003392.7	c.*1869C>T		3_prime_UTR_variant	5/5	ENST00000264634.9	NP_003383.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WNT5A	ENST00000264634.9	c.*1869C>T		3_prime_UTR_variant	5/5	1	NM_003392.7	ENSP00000264634	P1
WNT5A	ENST00000474267.5	c.*1869C>T		3_prime_UTR_variant	6/6	5		ENSP00000417310	P1

Frequencies

GnomAD3 genomes AF: 0.0750 AC: 11339 AN: 151200 Hom.: 735 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0774

Gnomad ASJ AF: 0.0588

Gnomad EAS AF: 0.0989

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.0210

Gnomad MID AF: 0.106

Gnomad NFE AF: 0.0230

Gnomad OTH AF: 0.0761

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0751 AC: 11369 AN: 151286 Hom.: 738 Cov.: 32 AF XY: 0.0776 AC XY: 5726 AN XY: 73788

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.0777

Gnomad4 ASJ AF: 0.0588

Gnomad4 EAS AF: 0.0991

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.0210

Gnomad4 NFE AF: 0.0230

Gnomad4 OTH AF: 0.0766

Alfa AF: 0.0518 Hom.: 93

Bravo AF: 0.0811

Asia WGS AF: 0.176 AC: 611 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 21, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.6
DANN	Benign	0.47

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

Other links and lift over

dbSNP: rs3732750; hg19: chr3-55502251;