Variant 1-160419212-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PP3_ModerateBP6_ModerateBS2

The NM_020335.3(VANGL2):c.403C>T(p.Arg135Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000085 in 1,611,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000089 ( 0 hom. )

Consequence

VANGL2
NM_020335.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.95

Variant links:

Genes affected

VANGL2 (HGNC:15511): (VANGL planar cell polarity protein 2) The protein encoded by this gene is a membrane protein involved in the regulation of planar cell polarity, especially in the stereociliary bundles of the cochlea. The encoded protein transmits directional signals to individual cells or groups of cells in epithelial sheets. This protein is also involved in the development of the neural plate. [provided by RefSeq, Sep 2011]

VANGL2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.858

BP6

Variant 1-160419212-C-T is Benign according to our data. Variant chr1-160419212-C-T is described in ClinVar as [Benign]. Clinvar id is 2672275.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VANGL2	NM_020335.3 linkuse as main transcript	c.403C>T	p.Arg135Trp	missense_variant	4/8	ENST00000368061.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VANGL2	ENST00000368061.3 linkuse as main transcript	c.403C>T	p.Arg135Trp	missense_variant	4/8	2	NM_020335.3	P1
VANGL2	ENST00000696602.1 linkuse as main transcript	c.547C>T	p.Arg183Trp	missense_variant	4/8

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000890

AC:

AN:

247284

Hom.:

AF XY:

0.000119

AC XY:

AN XY:

134078

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:

0.000178

Gnomad OTH exome

AF:

0.000329

GnomAD4 exome

AF:

0.0000891

AC:

130

AN:

1459638

Hom.:

Cov.:

AF XY:

0.0000881

AC XY:

AN XY:

726266

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

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:

0.0000989

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000419

Hom.:

Bravo

AF:

0.0000529

ExAC

AF:

0.0000989

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Neural tube defect

Benign:1

Benign, criteria provided, single submitter

research

Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center

Dec 12, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Pathogenic

0.27

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.75

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.93

LIST_S2

Pathogenic

0.98

M_CAP

Uncertain

0.11

MetaRNN

Pathogenic

0.86

MetaSVM

Uncertain

0.21

MutationAssessor

Benign

2.0

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-3.1

REVEL

Pathogenic

0.69

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.014

Polyphen

1.0

Vest4

0.89

MVP

0.78

MPC

1.4

ClinPred

0.66

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.49

gMVP

0.80

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