rs2896218

Positions:

• chr7-117279924-G-A

Variant summary

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

The NM_003391.3(WNT2):​c.854-1540C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 151,932 control chromosomes in the GnomAD database, including 27,830 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 0.60 (27830 hom., cov: 32)
• Consequence: WNT2 NM_003391.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.419

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 (EAS) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WNT2	NM_003391.3	c.854-1540C>T		intron_variant		ENST00000265441.8
WNT2	NR_024047.2	n.859-1540C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNT2	ENST00000265441.8	c.854-1540C>T		intron_variant		1	NM_003391.3	P1
WNT2	ENST00000449446.5	c.*457-1540C>T		intron_variant, NMD_transcript_variant		3
WNT2	ENST00000647844.1	c.*769-1540C>T		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91789 AN: 151814 Hom.: 27807 Cov.: 32

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.689

Gnomad SAS AF: 0.650

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.624

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

GnomAD4 genome AF: 0.605 AC: 91852 AN: 151932 Hom.: 27830 Cov.: 32 AF XY: 0.609 AC XY: 45231 AN XY: 74246

Gnomad4 AFR AF: 0.624

Gnomad4 AMR AF: 0.656

Gnomad4 ASJ AF: 0.585

Gnomad4 EAS AF: 0.689

Gnomad4 SAS AF: 0.649

Gnomad4 FIN AF: 0.593

Gnomad4 NFE AF: 0.575

Gnomad4 OTH AF: 0.618

Alfa AF: 0.587 Hom.: 35964

Bravo AF: 0.611

Asia WGS AF: 0.686 AC: 2380 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	0.66
DANN	Benign	0.44

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: rs2896218; hg19: chr7-116919978;