3-55468081-C-T

Position:

• chr3-55468081-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_003392.7(WNT5A):​c.*2011G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0079 in 144,140 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0079 (6 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: WNT5A NM_003392.7 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.82

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 3-55468081-C-T is Benign according to our data. Variant chr3-55468081-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1712780.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 1139 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WNT5A	NM_003392.7	c.*2011G>A		3_prime_UTR_variant	5/5	ENST00000264634.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNT5A	ENST00000264634.9	c.*2011G>A		3_prime_UTR_variant	5/5	1	NM_003392.7	P1
WNT5A	ENST00000474267.5	c.*2011G>A		3_prime_UTR_variant	6/6	5		P1

Frequencies

GnomAD3 genomes AF: 0.00791 AC: 1139 AN: 144036 Hom.: 6 Cov.: 31

Gnomad AFR AF: 0.00228

Gnomad AMI AF: 0.0411

Gnomad AMR AF: 0.00388

Gnomad ASJ AF: 0.00378

Gnomad EAS AF: 0.000204

Gnomad SAS AF: 0.00219

Gnomad FIN AF: 0.0215

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0111

Gnomad OTH AF: 0.00854

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 FIN exome AF: 0.00

GnomAD4 genome AF: 0.00790 AC: 1139 AN: 144140 Hom.: 6 Cov.: 31 AF XY: 0.00834 AC XY: 578 AN XY: 69308

Gnomad4 AFR AF: 0.00227

Gnomad4 AMR AF: 0.00387

Gnomad4 ASJ AF: 0.00378

Gnomad4 EAS AF: 0.000204

Gnomad4 SAS AF: 0.00197

Gnomad4 FIN AF: 0.0215

Gnomad4 NFE AF: 0.0111

Gnomad4 OTH AF: 0.00847

Alfa AF: 0.00902 Hom.: 0

Bravo AF: 0.00655

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 19, 2021

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	1.1
DANN	Benign	0.78

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: rs115634773; hg19: chr3-55502109;