rs648872

Variant names:

• chr3-55485829-G-A
• rs648872
• NM_003392.7:c.6+1151C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-55485829-G-A
• chr3-55485829-G-C
• chr3-55485829-G-T

Variant summary

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

The NM_003392.7(WNT5A):​c.6+1151C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,098 control chromosomes in the GnomAD database, including 3,363 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 0.20 (3363 hom., cov: 32)
• Consequence: WNT5A NM_003392.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.650
• Publications: 11 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT5A	NM_003392.7	c.6+1151C>T		intron_variant	Intron 1 of 4	ENST00000264634.9	NP_003383.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT5A	ENST00000264634.9	c.6+1151C>T		intron_variant	Intron 1 of 4	1	NM_003392.7	ENSP00000264634.4
WNT5A	ENST00000474267.5	c.6+1151C>T		intron_variant	Intron 2 of 5	5		ENSP00000417310.1

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30297 AN: 151980 Hom.: 3365 Cov.: 32

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.0584

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.199 AC: 30302 AN: 152098 Hom.: 3363 Cov.: 32 AF XY: 0.199 AC XY: 14804 AN XY: 74354

African (AFR) AF: 0.290 AC: 12036 AN: 41474

American (AMR) AF: 0.136 AC: 2084 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 784 AN: 3472

East Asian (EAS) AF: 0.0586 AC: 303 AN: 5172

South Asian (SAS) AF: 0.162 AC: 782 AN: 4814

European-Finnish (FIN) AF: 0.232 AC: 2455 AN: 10568

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.166 AC: 11262 AN: 67984

Other (OTH) AF: 0.177 AC: 375 AN: 2114

Alfa AF: 0.172 Hom.: 10253

Bravo AF: 0.196

Asia WGS AF: 0.123 AC: 428 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.0
DANN	Benign	0.64
PhyloP100		-0.65
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: rs648872; hg19: chr3-55519857;