chr1-160420452-A-G
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_020335.3(VANGL2):c.842A>G(p.His281Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000309 in 1,613,036 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00031 ( 3 hom. )
Consequence
VANGL2
NM_020335.3 missense
NM_020335.3 missense
Scores
1
18
Clinical Significance
Conservation
PhyloP100: 1.63
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 Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.012551099).
BP6
?
Variant 1-160420452-A-G is Benign according to our data. Variant chr1-160420452-A-G is described in ClinVar as [Benign]. Clinvar id is 3050384.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAd at 49 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VANGL2 | NM_020335.3 | c.842A>G | p.His281Arg | missense_variant | 5/8 | ENST00000368061.3 | |
VANGL2 | XM_005245357.2 | c.842A>G | p.His281Arg | missense_variant | 6/9 | ||
VANGL2 | XM_011509804.2 | c.842A>G | p.His281Arg | missense_variant | 5/8 | ||
VANGL2 | XM_047426020.1 | c.842A>G | p.His281Arg | missense_variant | 5/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VANGL2 | ENST00000368061.3 | c.842A>G | p.His281Arg | missense_variant | 5/8 | 2 | NM_020335.3 | P1 | |
VANGL2 | ENST00000696602.1 | c.986A>G | p.His329Arg | missense_variant | 5/8 | ||||
VANGL2 | ENST00000483408.1 | n.118-600A>G | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000324 AC: 49AN: 151146Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000561 AC: 141AN: 251494Hom.: 1 AF XY: 0.000530 AC XY: 72AN XY: 135920
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GnomAD4 exome AF: 0.000307 AC: 449AN: 1461890Hom.: 3 Cov.: 32 AF XY: 0.000318 AC XY: 231AN XY: 727248
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GnomAD4 genome ? AF: 0.000324 AC: 49AN: 151146Hom.: 0 Cov.: 32 AF XY: 0.000271 AC XY: 20AN XY: 73756
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
VANGL2-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 10, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MVP
MPC
ClinPred
T
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