chr1-160415821-C-T

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

2

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]

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
VANGL2NM_020335.3 linkc.-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
VANGL2ENST00000368061 linkc.-17C>T 5_prime_UTR_variant Exon 2 of 8 2 NM_020335.3 ENSP00000357040.2 Q9ULK5
VANGL2ENST00000696602.1 linkc.128C>T p.Ala43Val missense_variant Exon 2 of 8 ENSP00000512747.1 A0A8Q3SIN7

Frequencies

GnomAD3 genomes
AF:
0.000184
AC:
28
AN:
152230
Hom.:
0
Cov.:
32
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:
47
AN:
239662
Hom.:
0
AF XY:
0.000169
AC XY:
22
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.:
0
Cov.:
31
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:
28
AN:
152230
Hom.:
0
Cov.:
32
AF XY:
0.0000941
AC XY:
7
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.:
0
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
21
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.

Other links and lift over

dbSNP: rs372328442; hg19: chr1-160385611; COSMIC: COSV63605527; COSMIC: COSV63605527; API