chr7-117286578-C-G

Variant names:

• chr7-117286578-C-G
• rs3729629
• NM_003391.3:c.854-8194G>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_003391.3(WNT2):​c.854-8194G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 151,980 control chromosomes in the GnomAD database, including 19,277 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 0.50 (19277 hom., cov: 31)
• Consequence: WNT2 NM_003391.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20
• Publications: 9 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.53 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT2	NM_003391.3	MANE Select	c.854-8194G>C		intron	N/A	NP_003382.1
	WNT2	NR_024047.2		n.859-8194G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT2	ENST00000265441.8	TSL:1 MANE Select	c.854-8194G>C		intron	N/A	ENSP00000265441.3
	WNT2	ENST00000950642.1		c.563-8194G>C		intron	N/A	ENSP00000620701.1
	WNT2	ENST00000449446.5	TSL:3	n.*457-8194G>C		intron	N/A	ENSP00000389643.1

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75792 AN: 151860 Hom.: 19262 Cov.: 31

Gnomad AFR AF: 0.536

Gnomad AMI AF: 0.597

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.493

Gnomad OTH AF: 0.516

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

GnomAD4 genome AF: 0.499 AC: 75840 AN: 151980 Hom.: 19277 Cov.: 31 AF XY: 0.501 AC XY: 37180 AN XY: 74282

African (AFR) AF: 0.536 AC: 22207 AN: 41436

American (AMR) AF: 0.436 AC: 6662 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.513 AC: 1778 AN: 3468

East Asian (EAS) AF: 0.329 AC: 1697 AN: 5158

South Asian (SAS) AF: 0.315 AC: 1513 AN: 4810

European-Finnish (FIN) AF: 0.633 AC: 6676 AN: 10552

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.493 AC: 33506 AN: 67964

Other (OTH) AF: 0.515 AC: 1087 AN: 2110

Alfa AF: 0.497 Hom.: 2360

Bravo AF: 0.489

Asia WGS AF: 0.369 AC: 1281 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	19
DANN	Benign	0.73
PhyloP100		1.2
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: rs3729629; hg19: chr7-116926632;