rs2228946

Positions:

• chr7-117278031-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_003391.3(WNT2):​c.*124G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 1,121,734 control chromosomes in the GnomAD database, including 24,899 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 0.23 (4530 hom., cov: 33)
  • Exomes 𝑓: 0.20 (20369 hom.)
• Consequence: WNT2 NM_003391.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.25

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WNT2	NM_003391.3	c.*124G>A		3_prime_UTR_variant	5/5	ENST00000265441.8
WNT2	NR_024047.2	n.1212G>A		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNT2	ENST00000265441.8	c.*124G>A		3_prime_UTR_variant	5/5	1	NM_003391.3	P1
WNT2	ENST00000449446.5	c.*810G>A		3_prime_UTR_variant, NMD_transcript_variant	5/5	3
WNT2	ENST00000647844.1	c.*1122G>A		3_prime_UTR_variant, NMD_transcript_variant	6/6

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35190 AN: 152018 Hom.: 4526 Cov.: 33

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.0156

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.203

GnomAD4 exome AF: 0.196 AC: 190258 AN: 969598 Hom.: 20369 Cov.: 13 AF XY: 0.195 AC XY: 94567 AN XY: 485414

Gnomad4 AFR exome AF: 0.336

Gnomad4 AMR exome AF: 0.121

Gnomad4 ASJ exome AF: 0.206

Gnomad4 EAS exome AF: 0.0150

Gnomad4 SAS exome AF: 0.112

Gnomad4 FIN exome AF: 0.176

Gnomad4 NFE exome AF: 0.212

Gnomad4 OTH exome AF: 0.191

GnomAD4 genome AF: 0.232 AC: 35230 AN: 152136 Hom.: 4530 Cov.: 33 AF XY: 0.224 AC XY: 16690 AN XY: 74386

Gnomad4 AFR AF: 0.329

Gnomad4 AMR AF: 0.157

Gnomad4 ASJ AF: 0.204

Gnomad4 EAS AF: 0.0163

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.200

Alfa AF: 0.223 Hom.: 5378

Bravo AF: 0.236

Asia WGS AF: 0.0790 AC: 277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	14
DANN	Benign	0.86

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: rs2228946; hg19: chr7-116918085;