rs733154

chr7-117278857-A-Gchr7-117278857-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003391.3(WNT2):c.854-473T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 152,014 control chromosomes in the GnomAD database, including 16,516 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.46 (16516 hom., cov: 32)
• Consequence: WNT2 NM_003391.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0200

Genes affected

WNT2 (HGNC:12780): (Wnt family member 2) This gene is a member of the WNT gene family. 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. Alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WNT2	NM_003391.3	c.854-473T>C		intron_variant		ENST00000265441.8
WNT2	NR_024047.2	n.859-473T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNT2	ENST00000265441.8	c.854-473T>C		intron_variant		1	NM_003391.3	P1
WNT2	ENST00000449446.5	c.*457-473T>C		intron_variant, NMD_transcript_variant		3
WNT2	ENST00000647844.1	c.*769-473T>C		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70174 AN: 151896 Hom.: 16522 Cov.: 32

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.484

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.555

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.494

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

GnomAD4 genome AF: 0.462 AC: 70179 AN: 152014 Hom.: 16516 Cov.: 32 AF XY: 0.462 AC XY: 34337 AN XY: 74292

Gnomad4 AFR AF: 0.425

Gnomad4 AMR AF: 0.435

Gnomad4 ASJ AF: 0.508

Gnomad4 EAS AF: 0.245

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.555

Gnomad4 NFE AF: 0.497

Gnomad4 OTH AF: 0.490

Alfa AF: 0.482 Hom.: 3603

Bravo AF: 0.453

Asia WGS AF: 0.282 AC: 983 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.3
Dann	Benign	0.50

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: rs733154; hg19: chr7-116918911;