chr3-55468138-TAA-T

Position:

• chr3-55468138-TAA-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BA1

The NM_003392.7(WNT5A):​c.*1952_*1953del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.13 (1311 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: WNT5A NM_003392.7 3_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 0.330

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 -9 ACMG points.

• BP6: Variant 3-55468138-TAA-T is Benign according to our data. Variant chr3-55468138-TAA-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 346241.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1}.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNT5A	NM_003392.7	c.*1952_*1953del		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.*1952_*1953del		3_prime_UTR_variant	5/5	1	NM_003392.7	ENSP00000264634	P1
WNT5A	ENST00000474267.5	c.*1952_*1953del		3_prime_UTR_variant	6/6	5		ENSP00000417310	P1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 17898 AN: 133890 Hom.: 1312 Cov.: 0

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.153

Gnomad AMR AF: 0.0824

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.0746

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.0981

Gnomad MID AF: 0.115

Gnomad NFE AF: 0.0981

Gnomad OTH AF: 0.135

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.134 AC: 17899 AN: 133900 Hom.: 1311 Cov.: 0 AF XY: 0.132 AC XY: 8407 AN XY: 63648

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.0821

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.0746

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.0981

Gnomad4 NFE AF: 0.0981

Gnomad4 OTH AF: 0.134

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

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 Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 17, 2021

- -

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: rs78756487; hg19: chr3-55502166;