3-55467363-TC-T

Variant names:

• chr3-55467363-TC-T
• rs142609857
• NM_003392.7:c.*2728delG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_003392.7(WNT5A):​c.*2728delG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000021 (0 hom., cov: 22)
  • Exomes 𝑓: 0.0075 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: WNT5A NM_003392.7 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.792
• Publications: 0 publications found

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]

WNT5A Gene-Disease associations (from GenCC):

• autosomal dominant Robinow syndrome 1

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Illumina, Ambry Genetics
• autosomal dominant Robinow syndrome

  Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003392.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT5A	NM_003392.7	MANE Select	c.*2728delG		3_prime_UTR	Exon 5 of 5	NP_003383.4
	WNT5A	NM_001256105.1		c.*2728delG		3_prime_UTR	Exon 5 of 5	NP_001243034.1	P41221-2
	WNT5A	NM_001377271.1		c.*2728delG		3_prime_UTR	Exon 5 of 5	NP_001364200.1	P41221-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT5A	ENST00000264634.9	TSL:1 MANE Select	c.*2728delG		3_prime_UTR	Exon 5 of 5	ENSP00000264634.4	P41221-1
	WNT5A	ENST00000474267.5	TSL:5	c.*2728delG		3_prime_UTR	Exon 6 of 6	ENSP00000417310.1	P41221-1

Frequencies

GnomAD3 genomes AF: 0.0000213 AC: 2 AN: 93878 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000447

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00754 AC: 3 AN: 398 Hom.: 0 Cov.: 0 AF XY: 0.00813 AC XY: 2 AN XY: 246

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00761 AC: 3 AN: 394

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.00 AC: 0 AN: 4

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000213 AC: 2 AN: 93878 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 44824

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26996

American (AMR) AF: 0.00 AC: 0 AN: 6936

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2438

East Asian (EAS) AF: 0.00 AC: 0 AN: 2654

South Asian (SAS) AF: 0.00 AC: 0 AN: 2486

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5670

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 200

European-Non Finnish (NFE) AF: 0.0000447 AC: 2 AN: 44714

Other (OTH) AF: 0.00 AC: 0 AN: 1236

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000000000983081), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Autosomal dominant Robinow syndrome 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.79

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

Other links and lift over

dbSNP: rs142609857; hg19: chr3-55501391;