chr3-55468650-GTA-G

Position:

• chr3-55468650-GTA-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_003392.7(WNT5A):​c.*1440_*1441del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000808 in 147,188 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00080 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0088 (0 hom.)
• Consequence: WNT5A NM_003392.7 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.19

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 118 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WNT5A	NM_003392.7	c.*1440_*1441del		3_prime_UTR_variant	5/5	ENST00000264634.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNT5A	ENST00000264634.9	c.*1440_*1441del		3_prime_UTR_variant	5/5	1	NM_003392.7	P1
WNT5A	ENST00000474267.5	c.*1440_*1441del		3_prime_UTR_variant	6/6	5		P1

Frequencies

GnomAD3 genomes AF: 0.000796 AC: 117 AN: 147058 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00168

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000341

Gnomad ASJ AF: 0.00117

Gnomad EAS AF: 0.00470

Gnomad SAS AF: 0.000212

Gnomad FIN AF: 0.000226

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000165

Gnomad OTH AF: 0.000993

GnomAD4 exome AF: 0.00877 AC: 1 AN: 114 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 74

Gnomad4 FIN exome AF: 0.00909

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.000802 AC: 118 AN: 147074 Hom.: 0 Cov.: 32 AF XY: 0.000839 AC XY: 60 AN XY: 71542

Gnomad4 AFR AF: 0.00171

Gnomad4 AMR AF: 0.000341

Gnomad4 ASJ AF: 0.00117

Gnomad4 EAS AF: 0.00471

Gnomad4 SAS AF: 0.000213

Gnomad4 FIN AF: 0.000226

Gnomad4 NFE AF: 0.000165

Gnomad4 OTH AF: 0.000988

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Autosomal dominant Robinow syndrome 1 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs374828022; hg19: chr3-55502678;