rs556874

Variant names:

• chr3-55473253-T-C
• rs556874
• NM_003392.7:c.684+1084A>G

Variant summary

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

The NM_003392.7(WNT5A):​c.684+1084A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 152,030 control chromosomes in the GnomAD database, including 27,951 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 0.60 (27951 hom., cov: 32)
• Consequence: WNT5A NM_003392.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.833
• Publications: 10 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: Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT5A	NM_003392.7	c.684+1084A>G		intron_variant	Intron 4 of 4	ENST00000264634.9	NP_003383.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT5A	ENST00000264634.9	c.684+1084A>G		intron_variant	Intron 4 of 4	1	NM_003392.7	ENSP00000264634.4
WNT5A	ENST00000474267.5	c.684+1084A>G		intron_variant	Intron 5 of 5	5		ENSP00000417310.1
WNT5A	ENST00000497027.5	c.639+1084A>G		intron_variant	Intron 4 of 4	2		ENSP00000420104.1

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90572 AN: 151912 Hom.: 27917 Cov.: 32

Gnomad AFR AF: 0.743

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.593

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.622

Gnomad FIN AF: 0.599

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.580

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

GnomAD4 genome AF: 0.596 AC: 90661 AN: 152030 Hom.: 27951 Cov.: 32 AF XY: 0.595 AC XY: 44223 AN XY: 74310

African (AFR) AF: 0.743 AC: 30820 AN: 41470

American (AMR) AF: 0.460 AC: 7031 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.593 AC: 2060 AN: 3472

East Asian (EAS) AF: 0.328 AC: 1691 AN: 5158

South Asian (SAS) AF: 0.625 AC: 3010 AN: 4818

European-Finnish (FIN) AF: 0.599 AC: 6329 AN: 10566

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.557 AC: 37875 AN: 67950

Other (OTH) AF: 0.578 AC: 1220 AN: 2110

Alfa AF: 0.569 Hom.: 20139

Bravo AF: 0.590

Asia WGS AF: 0.508 AC: 1770 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.6
DANN	Benign	0.61
PhyloP100		0.83
Mutation Taster		=100/0	polymorphism (auto)

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: rs556874; hg19: chr3-55507281;