chr1-160419317-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3
The NM_020335.3(VANGL2):c.508C>T(p.Arg170Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000435 in 1,609,268 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
VANGL2
NM_020335.3 missense
NM_020335.3 missense
Scores
3
11
5
Clinical Significance
Conservation
PhyloP100: 2.97
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.774
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VANGL2 | NM_020335.3 | c.508C>T | p.Arg170Trp | missense_variant | 4/8 | ENST00000368061.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VANGL2 | ENST00000368061.3 | c.508C>T | p.Arg170Trp | missense_variant | 4/8 | 2 | NM_020335.3 | P1 | |
VANGL2 | ENST00000696602.1 | c.652C>T | p.Arg218Trp | missense_variant | 4/8 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152220Hom.: 0 Cov.: 31
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GnomAD4 exome AF: 0.00000275 AC: 4AN: 1457048Hom.: 0 Cov.: 32 AF XY: 0.00000276 AC XY: 2AN XY: 725166
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152220Hom.: 0 Cov.: 31 AF XY: 0.0000134 AC XY: 1AN XY: 74360
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 30, 2021 | The c.508C>T (p.R170W) alteration is located in exon 4 (coding exon 3) of the VANGL2 gene. This alteration results from a C to T substitution at nucleotide position 508, causing the arginine (R) at amino acid position 170 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
D
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Loss of methylation at R170 (P = 0.0388);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at