3-55468138-TAAAAAAA-TAAAAAAAAAA

Variant names:

• chr3-55468138-T-TAAA
• rs78756487
• NM_003392.7:c.*1951_*1953dupTTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_003392.7(WNT5A):​c.*1951_*1953dupTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.035 (123 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: WNT5A NM_003392.7 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0260
• 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 -10 ACMG points.

• BP6: Variant 3-55468138-T-TAAA is Benign according to our data. Variant chr3-55468138-T-TAAA is described in ClinVar as Likely_benign. ClinVar VariationId is 1325973.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0345 (4622/133898) while in subpopulation NFE AF = 0.0514 (3245/63076). AF 95% confidence interval is 0.05. There are 123 homozygotes in GnomAd4. There are 2162 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 4622 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.*1951_*1953dupTTT		3_prime_UTR	Exon 5 of 5	NP_003383.4
	WNT5A	NM_001256105.1		c.*1951_*1953dupTTT		3_prime_UTR	Exon 5 of 5	NP_001243034.1	P41221-2
	WNT5A	NM_001377271.1		c.*1951_*1953dupTTT		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.*1951_*1953dupTTT		3_prime_UTR	Exon 5 of 5	ENSP00000264634.4	P41221-1
	WNT5A	ENST00000474267.5	TSL:5	c.*1951_*1953dupTTT		3_prime_UTR	Exon 6 of 6	ENSP00000417310.1	P41221-1

Frequencies

GnomAD3 genomes AF: 0.0345 AC: 4621 AN: 133890 Hom.: 123 Cov.: 0

Gnomad AFR AF: 0.0116

Gnomad AMI AF: 0.0472

Gnomad AMR AF: 0.0223

Gnomad ASJ AF: 0.0228

Gnomad EAS AF: 0.000433

Gnomad SAS AF: 0.0275

Gnomad FIN AF: 0.0641

Gnomad MID AF: 0.00719

Gnomad NFE AF: 0.0514

Gnomad OTH AF: 0.0243

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0345 AC: 4622 AN: 133898 Hom.: 123 Cov.: 0 AF XY: 0.0340 AC XY: 2162 AN XY: 63658

African (AFR) AF: 0.0116 AC: 427 AN: 36828

American (AMR) AF: 0.0223 AC: 293 AN: 13162

Ashkenazi Jewish (ASJ) AF: 0.0228 AC: 75 AN: 3284

East Asian (EAS) AF: 0.000435 AC: 2 AN: 4600

South Asian (SAS) AF: 0.0277 AC: 113 AN: 4086

European-Finnish (FIN) AF: 0.0641 AC: 380 AN: 5924

Middle Eastern (MID) AF: 0.00794 AC: 2 AN: 252

European-Non Finnish (NFE) AF: 0.0514 AC: 3245 AN: 63076

Other (OTH) AF: 0.0242 AC: 44 AN: 1818

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.026
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs78756487; hg19: chr3-55502166;