chr1-160419212-C-T
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PP3_ModerateBP6_ModerateBS2
The NM_020335.3(VANGL2):c.403C>T(p.Arg135Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000085 in 1,611,818 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 Benign (★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000089 ( 0 hom. )
Consequence
VANGL2
NM_020335.3 missense
NM_020335.3 missense
Scores
6
10
3
Clinical Significance
Conservation
PhyloP100: 2.95
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 Likely_benign. Variant got -4 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.858
BP6
Variant 1-160419212-C-T is Benign according to our data. Variant chr1-160419212-C-T is described in ClinVar as [Benign]. Clinvar id is 2672275.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 7 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VANGL2 | NM_020335.3 | c.403C>T | p.Arg135Trp | missense_variant | 4/8 | ENST00000368061.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VANGL2 | ENST00000368061.3 | c.403C>T | p.Arg135Trp | missense_variant | 4/8 | 2 | NM_020335.3 | P1 | |
VANGL2 | ENST00000696602.1 | c.547C>T | p.Arg183Trp | missense_variant | 4/8 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152180Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000890 AC: 22AN: 247284Hom.: 0 AF XY: 0.000119 AC XY: 16AN XY: 134078
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GnomAD4 exome AF: 0.0000891 AC: 130AN: 1459638Hom.: 0 Cov.: 32 AF XY: 0.0000881 AC XY: 64AN XY: 726266
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GnomAD4 genome AF: 0.0000460 AC: 7AN: 152180Hom.: 0 Cov.: 31 AF XY: 0.0000403 AC XY: 3AN XY: 74354
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Neural tube defect Benign:1
Benign, criteria provided, single submitter | research | Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center | Dec 12, 2023 | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
D
MutationAssessor
Benign
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Pathogenic
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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