NM_003392.7:c.6+230A>C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT5A	NM_003392.7	c.6+230A>C		intron_variant	Intron 1 of 4	ENST00000264634.9	NP_003383.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT5A	ENST00000264634.9	c.6+230A>C		intron_variant	Intron 1 of 4	1	NM_003392.7	ENSP00000264634.4
WNT5A	ENST00000474267.5	c.6+230A>C		intron_variant	Intron 2 of 5	5		ENSP00000417310.1

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

Gnomad4 AFR AF: 0.940

Gnomad4 AMR AF: 0.589

Gnomad4 ASJ AF: 0.685

Gnomad4 EAS AF: 0.347

Gnomad4 SAS AF: 0.677

Gnomad4 FIN AF: 0.718

Gnomad4 NFE AF: 0.733

Gnomad4 OTH AF: 0.749

Alfa AF: 0.727 Hom.: 53421

Bravo AF: 0.758

Asia WGS AF: 0.560 AC: 1951 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	-0.86
CADD	Benign	3.7
DANN	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs566926; hg19: chr3-55520778;