rs62620048

Variant names:

• chr3-55470054-G-A
• rs62620048
• NM_003392.7:c.*38C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

The NM_003392.7(WNT5A):​c.*38C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00974 in 1,610,436 control chromosomes in the GnomAD database, including 97 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0073 (3 hom., cov: 33)
  • Exomes 𝑓: 0.010 (94 hom.)
• Consequence: WNT5A NM_003392.7 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.24
• Publications: 6 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 3-55470054-G-A is Benign according to our data. Variant chr3-55470054-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 346265.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 1110 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.*38C>T		3_prime_UTR	Exon 5 of 5	NP_003383.4
	WNT5A	NM_001256105.1		c.*38C>T		3_prime_UTR	Exon 5 of 5	NP_001243034.1	P41221-2
	WNT5A	NM_001377271.1		c.*38C>T		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.*38C>T		3_prime_UTR	Exon 5 of 5	ENSP00000264634.4	P41221-1
	WNT5A	ENST00000474267.5	TSL:5	c.*38C>T		3_prime_UTR	Exon 6 of 6	ENSP00000417310.1	P41221-1
	WNT5A	ENST00000497027.5	TSL:2	c.*38C>T		3_prime_UTR	Exon 5 of 5	ENSP00000420104.1	P41221-2

Frequencies

GnomAD3 genomes AF: 0.00729 AC: 1110 AN: 152206 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00217

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.00707

Gnomad ASJ AF: 0.0135

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0120

Gnomad OTH AF: 0.0105

GnomAD2 exomes AF: 0.00694 AC: 1729 AN: 249192 AF XY: 0.00679

Gnomad AFR exome AF: 0.00240

Gnomad AMR exome AF: 0.00481

Gnomad ASJ exome AF: 0.0112

Gnomad EAS exome AF: 0.000110

Gnomad FIN exome AF: 0.00250

Gnomad NFE exome AF: 0.0114

Gnomad OTH exome AF: 0.00760

GnomAD4 exome AF: 0.00999 AC: 14568 AN: 1458112 Hom.: 94 Cov.: 29 AF XY: 0.00979 AC XY: 7105 AN XY: 725650

African (AFR) AF: 0.00231 AC: 77 AN: 33402

American (AMR) AF: 0.00514 AC: 230 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.0125 AC: 326 AN: 26104

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39674

South Asian (SAS) AF: 0.000732 AC: 63 AN: 86118

European-Finnish (FIN) AF: 0.00336 AC: 179 AN: 53224

Middle Eastern (MID) AF: 0.0141 AC: 81 AN: 5756

European-Non Finnish (NFE) AF: 0.0118 AC: 13088 AN: 1108868

Other (OTH) AF: 0.00861 AC: 519 AN: 60256

GnomAD4 genome AF: 0.00729 AC: 1110 AN: 152324 Hom.: 3 Cov.: 33 AF XY: 0.00652 AC XY: 486 AN XY: 74488

African (AFR) AF: 0.00216 AC: 90 AN: 41574

American (AMR) AF: 0.00706 AC: 108 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0135 AC: 47 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00132 AC: 14 AN: 10610

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0120 AC: 815 AN: 68034

Other (OTH) AF: 0.0109 AC: 23 AN: 2114

Alfa AF: 0.0101 Hom.: 3

Bravo AF: 0.00836

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely 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	-0.40
CADD	Benign	16
DANN	Benign	0.87
PhyloP100		1.2
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: rs62620048; hg19: chr3-55504082;