3-55468650-G-GTA

Position:

• chr3-55468650-G-GTA

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_Supporting BS2

The NM_003392.7(WNT5A):​c.*1441_*1442insTA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00384 in 147,092 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.0038 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: WNT5A NM_003392.7 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• 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 -5 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00384 (565/147092) while in subpopulation EAS AF= 0.0292 (149/5098). AF 95% confidence interval is 0.0254. There are 5 homozygotes in gnomad4. There are 275 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High AC in GnomAd4 at 565 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNT5A	NM_003392.7	c.*1441_*1442insTA		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.*1441_*1442insTA		3_prime_UTR_variant	5/5	1	NM_003392.7	ENSP00000264634	P1
WNT5A	ENST00000474267.5	c.*1441_*1442insTA		3_prime_UTR_variant	6/6	5		ENSP00000417310	P1

Frequencies

GnomAD3 genomes AF: 0.00386 AC: 567 AN: 147076 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00332

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00218

Gnomad ASJ AF: 0.00234

Gnomad EAS AF: 0.0293

Gnomad SAS AF: 0.00212

Gnomad FIN AF: 0.000678

Gnomad MID AF: 0.00980

Gnomad NFE AF: 0.00313

Gnomad OTH AF: 0.00745

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 114 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 74

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00384 AC: 565 AN: 147092 Hom.: 5 Cov.: 32 AF XY: 0.00384 AC XY: 275 AN XY: 71544

Gnomad4 AFR AF: 0.00331

Gnomad4 AMR AF: 0.00218

Gnomad4 ASJ AF: 0.00234

Gnomad4 EAS AF: 0.0292

Gnomad4 SAS AF: 0.00192

Gnomad4 FIN AF: 0.000678

Gnomad4 NFE AF: 0.00315

Gnomad4 OTH AF: 0.00692

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

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

- -

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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;