rs566926

Variant names:

• chr3-55486750-T-G
• rs566926
• NM_003392.7:c.6+230A>C

Your query was ambiguous. Multiple possible variants found:

• chr3-55486750-T-G
• chr3-55486750-T-A
• chr3-55486750-T-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003392.7(WNT5A):​c.6+230A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.758 in 152,110 control chromosomes in the GnomAD database, including 45,319 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.76 (45319 hom., cov: 33)
• Consequence: WNT5A NM_003392.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.155
• Publications: 19 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 3-55486750-T-G is Benign according to our data. Variant chr3-55486750-T-G is described in ClinVar as Benign. ClinVar VariationId is 1259465.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.933 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.6+230A>C		intron	N/A	NP_003383.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT5A	ENST00000264634.9	TSL:1 MANE Select	c.6+230A>C		intron	N/A	ENSP00000264634.4	P41221-1
	WNT5A	ENST00000474267.5	TSL:5	c.6+230A>C		intron	N/A	ENSP00000417310.1	P41221-1

Frequencies

GnomAD3 genomes AF: 0.758 AC: 115248 AN: 151992 Hom.: 45265 Cov.: 33

Gnomad AFR AF: 0.940

Gnomad AMI AF: 0.730

Gnomad AMR AF: 0.589

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.718

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.733

Gnomad OTH AF: 0.753

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

GnomAD4 genome AF: 0.758 AC: 115357 AN: 152110 Hom.: 45319 Cov.: 33 AF XY: 0.752 AC XY: 55902 AN XY: 74352

African (AFR) AF: 0.940 AC: 39067 AN: 41546

American (AMR) AF: 0.589 AC: 9010 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.685 AC: 2380 AN: 3472

East Asian (EAS) AF: 0.347 AC: 1784 AN: 5140

South Asian (SAS) AF: 0.677 AC: 3266 AN: 4824

European-Finnish (FIN) AF: 0.718 AC: 7581 AN: 10560

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.733 AC: 49804 AN: 67954

Other (OTH) AF: 0.749 AC: 1581 AN: 2110

Alfa AF: 0.731 Hom.: 76446

Bravo AF: 0.758

Asia WGS AF: 0.560 AC: 1951 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.7
DANN	Benign	0.68
PhyloP100		-0.15
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: rs566926; hg19: chr3-55520778;