1-160420452-A-G

Variant summary

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

The NM_020335.3(VANGL2):c.842A>G(p.His281Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000309 in 1,613,036 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00031 ( 3 hom. )

Consequence

VANGL2
NM_020335.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.63

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012551099).

BP6

Variant 1-160420452-A-G is Benign according to our data. Variant chr1-160420452-A-G is described in ClinVar as [Benign]. Clinvar id is 3050384.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 49 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
VANGL2	NM_020335.3 linkuse as main transcript	c.842A>G	p.His281Arg	missense_variant	5/8	ENST00000368061.3
VANGL2	XM_005245357.2 linkuse as main transcript	c.842A>G	p.His281Arg	missense_variant	6/9
VANGL2	XM_011509804.2 linkuse as main transcript	c.842A>G	p.His281Arg	missense_variant	5/8
VANGL2	XM_047426020.1 linkuse as main transcript	c.842A>G	p.His281Arg	missense_variant	5/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
VANGL2	ENST00000368061.3 linkuse as main transcript	c.842A>G	p.His281Arg	missense_variant	5/8	2	NM_020335.3	P1
VANGL2	ENST00000696602.1 linkuse as main transcript	c.986A>G	p.His329Arg	missense_variant	5/8
VANGL2	ENST00000483408.1 linkuse as main transcript	n.118-600A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000324

AC:

AN:

151146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000487

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.0124

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000590

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000561

AC:

141

AN:

251494

Hom.:

AF XY:

0.000530

AC XY:

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.0117

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000141

Gnomad OTH exome

AF:

0.000977

GnomAD4 exome

AF:

0.000307

AC:

449

AN:

1461890

Hom.:

Cov.:

AF XY:

0.000318

AC XY:

231

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.0124

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000594

Gnomad4 OTH exome

AF:

0.000944

GnomAD4 genome

AF:

0.000324

AC:

AN:

151146

Hom.:

Cov.:

AF XY:

0.000271

AC XY:

AN XY:

73756

show subpopulations

Gnomad4 AFR

AF:

0.0000487

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.0124

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000590

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000664

Hom.:

Bravo

AF:

0.000382

ExAC

AF:

0.000395

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

VANGL2-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 10, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.26

Cadd

Benign

Dann

Benign

0.85

DEOGEN2

Benign

0.17

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.83

M_CAP

Benign

0.013

MetaRNN

Benign

0.013

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.63

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.70

PROVEAN

Benign

0.93

REVEL

Benign

0.26

Sift

Benign

0.82

Sift4G

Benign

0.70

Polyphen

0.036

Vest4

0.31

MVP

0.27

MPC

0.63

ClinPred

0.037

GERP RS

5.0

Varity_R

0.16

gMVP

0.45

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