7-117280916-T-C

Variant names:

• chr7-117280916-T-C
• rs916725
• NM_003391.3:c.854-2532A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003391.3(WNT2):​c.854-2532A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.633 in 151,528 control chromosomes in the GnomAD database, including 30,478 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 0.63 (30478 hom., cov: 32)
• Consequence: WNT2 NM_003391.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.447
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003391.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT2	NM_003391.3	MANE Select	c.854-2532A>G		intron	N/A	NP_003382.1
	WNT2	NR_024047.2		n.859-2532A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT2	ENST00000265441.8	TSL:1 MANE Select	c.854-2532A>G		intron	N/A	ENSP00000265441.3
	WNT2	ENST00000449446.5	TSL:3	n.*457-2532A>G		intron	N/A	ENSP00000389643.1
	WNT2	ENST00000647844.1		n.*769-2532A>G		intron	N/A	ENSP00000497695.1

Frequencies

GnomAD3 genomes AF: 0.633 AC: 95813 AN: 151410 Hom.: 30445 Cov.: 32

Gnomad AFR AF: 0.677

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.670

Gnomad ASJ AF: 0.592

Gnomad EAS AF: 0.725

Gnomad SAS AF: 0.660

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.641

Gnomad NFE AF: 0.594

Gnomad OTH AF: 0.643

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

GnomAD4 genome AF: 0.633 AC: 95888 AN: 151528 Hom.: 30478 Cov.: 32 AF XY: 0.637 AC XY: 47140 AN XY: 73996

African (AFR) AF: 0.677 AC: 27935 AN: 41280

American (AMR) AF: 0.671 AC: 10221 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.592 AC: 2054 AN: 3470

East Asian (EAS) AF: 0.725 AC: 3726 AN: 5140

South Asian (SAS) AF: 0.660 AC: 3165 AN: 4798

European-Finnish (FIN) AF: 0.611 AC: 6415 AN: 10492

Middle Eastern (MID) AF: 0.655 AC: 190 AN: 290

European-Non Finnish (NFE) AF: 0.594 AC: 40294 AN: 67808

Other (OTH) AF: 0.638 AC: 1343 AN: 2106

Alfa AF: 0.606 Hom.: 82722

Bravo AF: 0.642

Asia WGS AF: 0.711 AC: 2468 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.48
DANN	Benign	0.62
PhyloP100		-0.45
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: rs916725; hg19: chr7-116920970;