Variant rs12086448 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_020335.3(VANGL2):c.1137A>G(p.Lys379Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 1,613,826 control chromosomes in the GnomAD database, including 231,884 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.58 ( 26727 hom., cov: 31)

Exomes 𝑓: 0.53 ( 205157 hom. )

Consequence

VANGL2
NM_020335.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.12

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:

VANGL2 (HGNC:):

VANGL2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 1-160424115-A-G is Benign according to our data. Variant chr1-160424115-A-G is described in ClinVar as [Benign]. Clinvar id is 1684206.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.12 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VANGL2	NM_020335.3 linkuse as main transcript	c.1137A>G	p.Lys379Lys	synonymous_variant	7/8	ENST00000368061.3	NP_065068.1	Q9ULK5A8K4L6
VANGL2	XM_005245357.2 linkuse as main transcript	c.1137A>G	p.Lys379Lys	synonymous_variant	8/9		XP_005245414.1	Q9ULK5
VANGL2	XM_011509804.2 linkuse as main transcript	c.1137A>G	p.Lys379Lys	synonymous_variant	7/8		XP_011508106.1	Q9ULK5
VANGL2	XM_047426020.1 linkuse as main transcript	c.1137A>G	p.Lys379Lys	synonymous_variant	7/8		XP_047281976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
VANGL2	ENST00000368061.3 linkuse as main transcript	c.1137A>G	p.Lys379Lys	synonymous_variant	7/8	2	NM_020335.3	ENSP00000357040.2	Q9ULK5
VANGL2	ENST00000696602.1 linkuse as main transcript	c.1281A>G	p.Lys427Lys	synonymous_variant	7/8			ENSP00000512747.1	A0A8Q3SIN7
VANGL2	ENST00000483408.1 linkuse as main transcript	n.317A>G		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes

AF:

0.579

AC:

88005

AN:

151872

Hom.:

26713

Cov.:

show subpopulations

Gnomad AFR

AF:

0.764

Gnomad AMI

AF:

0.591

Gnomad AMR

AF:

0.489

Gnomad ASJ

AF:

0.478

Gnomad EAS

AF:

0.375

Gnomad SAS

AF:

0.616

Gnomad FIN

AF:

0.482

Gnomad MID

AF:

0.566

Gnomad NFE

AF:

0.521

Gnomad OTH

AF:

0.567

GnomAD3 exomes

AF:

0.511

AC:

128496

AN:

251378

Hom.:

34050

AF XY:

0.516

AC XY:

70085

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.768

Gnomad AMR exome

AF:

0.380

Gnomad ASJ exome

AF:

0.476

Gnomad EAS exome

AF:

0.367

Gnomad SAS exome

AF:

0.610

Gnomad FIN exome

AF:

0.483

Gnomad NFE exome

AF:

0.520

Gnomad OTH exome

AF:

0.503

GnomAD4 exome

AF:

0.527

AC:

769714

AN:

1461836

Hom.:

205157

Cov.:

AF XY:

0.528

AC XY:

383723

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.773

Gnomad4 AMR exome

AF:

0.399

Gnomad4 ASJ exome

AF:

0.476

Gnomad4 EAS exome

AF:

0.380

Gnomad4 SAS exome

AF:

0.605

Gnomad4 FIN exome

AF:

0.476

Gnomad4 NFE exome

AF:

0.527

Gnomad4 OTH exome

AF:

0.526

GnomAD4 genome

AF:

0.579

AC:

88064

AN:

151990

Hom.:

26727

Cov.:

AF XY:

0.576

AC XY:

42778

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.764

Gnomad4 AMR

AF:

0.489

Gnomad4 ASJ

AF:

0.478

Gnomad4 EAS

AF:

0.375

Gnomad4 SAS

AF:

0.615

Gnomad4 FIN

AF:

0.482

Gnomad4 NFE

AF:

0.521

Gnomad4 OTH

AF:

0.565

Alfa

AF:

0.545

Hom.:

17286

Bravo

AF:

0.585

Asia WGS

AF:

0.525

AC:

1824

AN:

3478

EpiCase

AF:

0.528

EpiControl

AF:

0.527

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Neural tube defect

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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