rs12497254

Variant names:

• chr3-55465636-G-A
• rs12497254
• NM_003392.7:c.*4456C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-55465636-G-A
• chr3-55465636-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003392.7(WNT5A):​c.*4456C>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 151,964 control chromosomes in the GnomAD database, including 15,132 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.44 (15132 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: WNT5A NM_003392.7 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.507
• Publications: 13 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

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.*4456C>T		downstream_gene	N/A	NP_003383.4
	WNT5A	NM_001256105.1		c.*4456C>T		downstream_gene	N/A	NP_001243034.1	P41221-2
	WNT5A	NM_001377271.1		c.*4456C>T		downstream_gene	N/A	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.*4456C>T		downstream_gene	N/A	ENSP00000264634.4	P41221-1
	WNT5A	ENST00000474267.5	TSL:5	c.*4456C>T		downstream_gene	N/A	ENSP00000417310.1	P41221-1

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66570 AN: 151846 Hom.: 15125 Cov.: 32

Gnomad AFR AF: 0.360

Gnomad AMI AF: 0.560

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.454

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

GnomAD4 genome AF: 0.438 AC: 66585 AN: 151964 Hom.: 15132 Cov.: 32 AF XY: 0.438 AC XY: 32547 AN XY: 74260

African (AFR) AF: 0.359 AC: 14890 AN: 41446

American (AMR) AF: 0.569 AC: 8696 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 1483 AN: 3470

East Asian (EAS) AF: 0.673 AC: 3471 AN: 5160

South Asian (SAS) AF: 0.372 AC: 1791 AN: 4814

European-Finnish (FIN) AF: 0.399 AC: 4207 AN: 10532

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.448 AC: 30459 AN: 67954

Other (OTH) AF: 0.454 AC: 957 AN: 2108

Alfa AF: 0.454 Hom.: 20788

Bravo AF: 0.451

Asia WGS AF: 0.494 AC: 1717 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.9
DANN	Benign	0.60
PhyloP100		0.51

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12497254; hg19: chr3-55499664;