3-55468138-TAAAAAAA-TAAAAA

Variant names:

• chr3-55468138-TAA-T
• rs78756487
• NM_003392.7:c.*1952_*1953delTT

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6 BA1

The NM_003392.7(WNT5A):​c.*1952_*1953delTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.13 (1311 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: WNT5A NM_003392.7 3_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 0.330
• Publications: 0 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 -9 ACMG points.

• BP6: Variant 3-55468138-TAA-T is Benign according to our data. Variant chr3-55468138-TAA-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 346241.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.218 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.*1952_*1953delTT		3_prime_UTR	Exon 5 of 5	NP_003383.4
	WNT5A	NM_001256105.1		c.*1952_*1953delTT		3_prime_UTR	Exon 5 of 5	NP_001243034.1	P41221-2
	WNT5A	NM_001377271.1		c.*1952_*1953delTT		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.*1952_*1953delTT		3_prime_UTR	Exon 5 of 5	ENSP00000264634.4	P41221-1
	WNT5A	ENST00000474267.5	TSL:5	c.*1952_*1953delTT		3_prime_UTR	Exon 6 of 6	ENSP00000417310.1	P41221-1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 17898 AN: 133890 Hom.: 1312 Cov.: 0

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.153

Gnomad AMR AF: 0.0824

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.0746

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.0981

Gnomad MID AF: 0.115

Gnomad NFE AF: 0.0981

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.134 AC: 17899 AN: 133900 Hom.: 1311 Cov.: 0 AF XY: 0.132 AC XY: 8407 AN XY: 63648

African (AFR) AF: 0.222 AC: 8172 AN: 36798

American (AMR) AF: 0.0821 AC: 1081 AN: 13162

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 553 AN: 3290

East Asian (EAS) AF: 0.0746 AC: 343 AN: 4598

South Asian (SAS) AF: 0.140 AC: 574 AN: 4094

European-Finnish (FIN) AF: 0.0981 AC: 583 AN: 5942

Middle Eastern (MID) AF: 0.127 AC: 32 AN: 252

European-Non Finnish (NFE) AF: 0.0981 AC: 6185 AN: 63076

Other (OTH) AF: 0.134 AC: 243 AN: 1820

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	-	Autosomal dominant Robinow syndrome 1 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.33
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: rs78756487; hg19: chr3-55502166; COSMIC: COSV52837001; COSMIC: COSV52837001;