Variant 7-117278181-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_003391.3(WNT2):c.1057A>G(p.Asn353Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00604 in 1,614,204 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0045 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0062 ( 36 hom. )

Consequence

WNT2
NM_003391.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.15

Variant links:

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]

WNT2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0045837164).

BP6

Variant 7-117278181-T-C is Benign according to our data. Variant chr7-117278181-T-C is described in ClinVar as [Benign]. Clinvar id is 719651.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 685 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WNT2	NM_003391.3 linkuse as main transcript	c.1057A>G	p.Asn353Asp	missense_variant	5/5	ENST00000265441.8
WNT2	NR_024047.2 linkuse as main transcript	n.1062A>G		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
WNT2	ENST00000265441.8 linkuse as main transcript	c.1057A>G	p.Asn353Asp	missense_variant	5/5	1	NM_003391.3	P1
WNT2	ENST00000449446.5 linkuse as main transcript	c.*660A>G		3_prime_UTR_variant, NMD_transcript_variant	5/5	3
WNT2	ENST00000647844.1 linkuse as main transcript	c.*972A>G		3_prime_UTR_variant, NMD_transcript_variant	6/6

Frequencies

GnomAD3 genomes

AF:

0.00450

AC:

685

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00125

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.000850

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00913

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00742

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00483

AC:

1213

AN:

251314

Hom.:

AF XY:

0.00480

AC XY:

652

AN XY:

135810

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.000896

Gnomad ASJ exome

AF:

0.00288

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0109

Gnomad NFE exome

AF:

0.00781

Gnomad OTH exome

AF:

0.00376

GnomAD4 exome

AF:

0.00620

AC:

9071

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00594

AC XY:

4323

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.000687

Gnomad4 AMR exome

AF:

0.000984

Gnomad4 ASJ exome

AF:

0.00203

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0114

Gnomad4 NFE exome

AF:

0.00723

Gnomad4 OTH exome

AF:

0.00490

GnomAD4 genome

AF:

0.00450

AC:

685

AN:

152318

Hom.:

Cov.:

AF XY:

0.00431

AC XY:

321

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00125

Gnomad4 AMR

AF:

0.000849

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00913

Gnomad4 NFE

AF:

0.00742

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00634

Hom.:

Bravo

AF:

0.00388

TwinsUK

AF:

0.00998

AC:

ALSPAC

AF:

0.00934

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00628

AC:

ExAC

AF:

0.00530

AC:

643

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00562

EpiControl

AF:

0.00605

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.36

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.069

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.92

MetaRNN

Benign

0.0046

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.69

MutationTaster

Benign

1.0

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.16

REVEL

Benign

0.14

Sift

Benign

0.036

Sift4G

Benign

0.33

Polyphen

0.019

Vest4

0.11

MVP

0.39

MPC

0.28

ClinPred

0.017

GERP RS

6.0

Varity_R

0.092

gMVP

0.096

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over