Genetic Variant VANGL2:c.-17C>T (chr1-160415821-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_020335.3(VANGL2):c.-17C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000193 in 1,610,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

VANGL2
NM_020335.3 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.45

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 1-160415821-C-T is Benign according to our data. Variant chr1-160415821-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3388087.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 28 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VANGL2	NM_020335.3 link	c.-17C>T		5_prime_UTR_variant	Exon 2 of 8	ENST00000368061.3	NP_065068.1	Q9ULK5A8K4L6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VANGL2	ENST00000368061 link	c.-17C>T		5_prime_UTR_variant	Exon 2 of 8	2	NM_020335.3	ENSP00000357040.2		Q9ULK5
VANGL2	ENST00000696602.1 link	c.128C>T	p.Ala43Val	missense_variant	Exon 2 of 8			ENSP00000512747.1		A0A8Q3SIN7

Frequencies

GnomAD3 genomes

AF:

0.000184

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000196

AC:

AN:

239662

Hom.:

AF XY:

0.000169

AC XY:

AN XY:

130022

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000594

Gnomad ASJ exome

AF:

0.000103

Gnomad EAS exome

AF:

0.000394

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000193

Gnomad NFE exome

AF:

0.000280

Gnomad OTH exome

AF:

0.000517

GnomAD4 exome

AF:

0.000194

AC:

283

AN:

1458178

Hom.:

Cov.:

AF XY:

0.000201

AC XY:

146

AN XY:

725008

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.0000454

Gnomad4 ASJ exome

AF:

0.0000386

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0000585

Gnomad4 FIN exome

AF:

0.000320

Gnomad4 NFE exome

AF:

0.000215

Gnomad4 OTH exome

AF:

0.000183

GnomAD4 genome

AF:

0.000184

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000545

Hom.:

Bravo

AF:

0.000159

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Oct 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

VANGL2: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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