Variant rs895560180 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_003391.3(WNT2):c.88A>T(p.Met30Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000371 in 1,456,430 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

WNT2
NM_003391.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.65

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:

CFTR (HGNC:1884): (CF transmembrane conductance regulator) This gene encodes a member of the ATP-binding cassette (ABC) transporter superfamily. The encoded protein functions as a chloride channel, making it unique among members of this protein family, and controls ion and water secretion and absorption in epithelial tissues. Channel activation is mediated by cycles of regulatory domain phosphorylation, ATP-binding by the nucleotide-binding domains, and ATP hydrolysis. Mutations in this gene cause cystic fibrosis, the most common lethal genetic disorder in populations of Northern European descent. The most frequently occurring mutation in cystic fibrosis, DeltaF508, results in impaired folding and trafficking of the encoded protein. Multiple pseudogenes have been identified in the human genome. [provided by RefSeq, Aug 2017]

CFTR links:

LOC105375467 (HGNC:):

LOC105375467 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.22030407).

BS2

High AC in GnomAdExome4 at 54 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT2	NM_003391.3 link	c.88A>T	p.Met30Leu	missense_variant	Exon 2 of 5	ENST00000265441.8	NP_003382.1	P09544A0A384MDX3
WNT2	NR_024047.2 link	n.157A>T		non_coding_transcript_exon_variant	Exon 2 of 5
LOC105375467	XR_007060645.1 link	n.80-1269T>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT2	ENST00000265441.8 link	c.88A>T	p.Met30Leu	missense_variant	Exon 2 of 5	1	NM_003391.3	ENSP00000265441.3		P09544

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000125

AC:

AN:

240660

Hom.:

AF XY:

0.00000768

AC XY:

AN XY:

130144

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000275

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000371

AC:

AN:

1456430

Hom.:

Cov.:

AF XY:

0.0000318

AC XY:

AN XY:

724176

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000486

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.010

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.34

T;T

Eigen

Benign

-0.19

Eigen_PC

Benign

0.051

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.84

T;D

M_CAP

Benign

0.016

MetaRNN

Benign

0.22

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.69

N;.

PrimateAI

Uncertain

0.53

PROVEAN

Benign

0.43

N;N

REVEL

Benign

0.26

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;.

Polyphen

0.0

B;.

Vest4

0.50

MutPred

0.41

Loss of catalytic residue at M30 (P = 0.0017);Loss of catalytic residue at M30 (P = 0.0017);

MVP

0.82

MPC

0.22

ClinPred

0.15

GERP RS

5.4

Varity_R

0.26

gMVP

0.81

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over