rs7622120

Variant names:

• chr3-55470702-A-G
• rs7622120
• NM_003392.7:c.685-152T>C

Your query was ambiguous. Multiple possible variants found:

• chr3-55470702-A-G
• chr3-55470702-A-T

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.685-152T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 152,162 control chromosomes in the GnomAD database, including 27,165 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.59 (27165 hom., cov: 33)
• Consequence: WNT5A NM_003392.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.371
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 3-55470702-A-G is Benign according to our data. Variant chr3-55470702-A-G is described in ClinVar as Benign. ClinVar VariationId is 1268922.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT5A	NM_003392.7	c.685-152T>C		intron_variant	Intron 4 of 4	ENST00000264634.9	NP_003383.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT5A	ENST00000264634.9	c.685-152T>C		intron_variant	Intron 4 of 4	1	NM_003392.7	ENSP00000264634.4
WNT5A	ENST00000474267.5	c.685-152T>C		intron_variant	Intron 5 of 5	5		ENSP00000417310.1
WNT5A	ENST00000497027.5	c.640-152T>C		intron_variant	Intron 4 of 4	2		ENSP00000420104.1

Frequencies

GnomAD3 genomes AF: 0.586 AC: 89166 AN: 152044 Hom.: 27130 Cov.: 33

Gnomad AFR AF: 0.744

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.595

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.568

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

GnomAD4 genome AF: 0.587 AC: 89257 AN: 152162 Hom.: 27165 Cov.: 33 AF XY: 0.586 AC XY: 43585 AN XY: 74384

African (AFR) AF: 0.744 AC: 30869 AN: 41500

American (AMR) AF: 0.445 AC: 6804 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.577 AC: 2000 AN: 3468

East Asian (EAS) AF: 0.325 AC: 1684 AN: 5188

South Asian (SAS) AF: 0.623 AC: 3003 AN: 4822

European-Finnish (FIN) AF: 0.595 AC: 6296 AN: 10574

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.541 AC: 36824 AN: 68006

Other (OTH) AF: 0.567 AC: 1195 AN: 2108

Alfa AF: 0.514 Hom.: 4336

Bravo AF: 0.580

Asia WGS AF: 0.506 AC: 1763 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.86
DANN	Benign	0.31
PhyloP100		-0.37
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: rs7622120; hg19: chr3-55504730; COSMIC: COSV107278779; COSMIC: COSV107278779;