3-55465912-T-TA

Variant names:

• chr3-55465912-T-TA
• rs56661203
• NM_003392.7:c.*4179dupT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_003392.7(WNT5A):​c.*4179dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00857 in 151,560 control chromosomes in the GnomAD database, including 26 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0086 (26 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: WNT5A NM_003392.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0370
• Publications: 1 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 3-55465912-T-TA is Benign according to our data. Variant chr3-55465912-T-TA is described in ClinVar as Benign. ClinVar VariationId is 346206.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00857 (1299/151560) while in subpopulation AFR AF = 0.0293 (1212/41376). AF 95% confidence interval is 0.0279. There are 26 homozygotes in GnomAd4. There are 603 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1299 AD gene.

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.*4179dupT		3_prime_UTR	Exon 5 of 5	NP_003383.4
	WNT5A	NM_001256105.1		c.*4179dupT		3_prime_UTR	Exon 5 of 5	NP_001243034.1	P41221-2
	WNT5A	NM_001377271.1		c.*4179dupT		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.*4179dupT		3_prime_UTR	Exon 5 of 5	ENSP00000264634.4	P41221-1
	WNT5A	ENST00000474267.5	TSL:5	c.*4179dupT		3_prime_UTR	Exon 6 of 6	ENSP00000417310.1	P41221-1

Frequencies

GnomAD3 genomes AF: 0.00856 AC: 1297 AN: 151440 Hom.: 26 Cov.: 33

Gnomad AFR AF: 0.0293

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00342

Gnomad ASJ AF: 0.00203

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000236

Gnomad OTH AF: 0.00580

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

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) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

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

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.00857 AC: 1299 AN: 151560 Hom.: 26 Cov.: 33 AF XY: 0.00814 AC XY: 603 AN XY: 74084

African (AFR) AF: 0.0293 AC: 1212 AN: 41376

American (AMR) AF: 0.00342 AC: 52 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.00203 AC: 7 AN: 3456

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000236 AC: 16 AN: 67836

Other (OTH) AF: 0.00574 AC: 12 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00977

ClinVar

ClinVar submissions

Significance: Benign

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		0.037
Mutation Taster		=100/0	polymorphism

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: rs56661203; hg19: chr3-55499940;