chr1-160420494-A-G
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_020335.3(VANGL2):āc.884A>Gā(p.Lys295Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000703 in 1,614,036 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.00036 ( 0 hom., cov: 32)
Exomes š: 0.00074 ( 3 hom. )
Consequence
VANGL2
NM_020335.3 missense
NM_020335.3 missense
Scores
1
8
10
Clinical Significance
Conservation
PhyloP100: 8.91
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.
BS2
High AC in GnomAd4 at 55 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VANGL2 | NM_020335.3 | c.884A>G | p.Lys295Arg | missense_variant | 5/8 | ENST00000368061.3 | |
VANGL2 | XM_005245357.2 | c.884A>G | p.Lys295Arg | missense_variant | 6/9 | ||
VANGL2 | XM_011509804.2 | c.884A>G | p.Lys295Arg | missense_variant | 5/8 | ||
VANGL2 | XM_047426020.1 | c.884A>G | p.Lys295Arg | missense_variant | 5/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VANGL2 | ENST00000368061.3 | c.884A>G | p.Lys295Arg | missense_variant | 5/8 | 2 | NM_020335.3 | P1 | |
VANGL2 | ENST00000696602.1 | c.1028A>G | p.Lys343Arg | missense_variant | 5/8 | ||||
VANGL2 | ENST00000483408.1 | n.118-558A>G | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.000362 AC: 55AN: 152026Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000398 AC: 100AN: 251494Hom.: 0 AF XY: 0.000361 AC XY: 49AN XY: 135920
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GnomAD4 exome AF: 0.000739 AC: 1080AN: 1461892Hom.: 3 Cov.: 32 AF XY: 0.000694 AC XY: 505AN XY: 727246
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GnomAD4 genome AF: 0.000362 AC: 55AN: 152144Hom.: 0 Cov.: 32 AF XY: 0.000309 AC XY: 23AN XY: 74376
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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 | Jun 07, 2022 | The c.884A>G (p.K295R) alteration is located in exon 5 (coding exon 4) of the VANGL2 gene. This alteration results from a A to G substitution at nucleotide position 884, causing the lysine (K) at amino acid position 295 to be replaced by an arginine (R). 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
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Uncertain
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Benign
T
Sift4G
Benign
T
Polyphen
D
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
DS_DG_spliceai
Position offset: 0
Find out detailed SpliceAI scores and Pangolin per-transcript scores at