3-55468138-T-TA

Variant summary

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

The NM_003392.7(WNT5A):c.*1953_*1954insT 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 0.37 (9554 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:2
• Conservation: PhyloP100: -0.0260

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-T-TA is Benign according to our data. Variant chr3-55468138-T-TA is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 346239.We mark this variant Likely_benign, oryginal submissions are: {Benign=2, Uncertain_significance=1}.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WNT5A	NM_003392.7	c.*1953_*1954insT		3_prime_UTR_variant	5/5	ENST00000264634.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNT5A	ENST00000264634.9	c.*1953_*1954insT		3_prime_UTR_variant	5/5	1	NM_003392.7	P1
WNT5A	ENST00000474267.5	c.*1953_*1954insT		3_prime_UTR_variant	6/6	5		P1

Frequencies

GnomAD3 genomes AF: 0.374 AC: 50011 AN: 133758 Hom.: 9560 Cov.: 0

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.530

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.592

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.378

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.383

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: 0.374 AC: 49995 AN: 133772 Hom.: 9554 Cov.: 0 AF XY: 0.371 AC XY: 23597 AN XY: 63608

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.366

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.591

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.370

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.383

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:2

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Autosomal dominant Robinow syndrome 1 Uncertain:1 Benign:1

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
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 16, 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;