rs199566606
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_198859.4(PRICKLE2):c.454G>A(p.Gly152Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000198 in 1,614,048 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000019 ( 0 hom. )
Consequence
PRICKLE2
NM_198859.4 missense
NM_198859.4 missense
Scores
6
8
Clinical Significance
Conservation
PhyloP100: 5.02
Genes affected
PRICKLE2 (HGNC:20340): (prickle planar cell polarity protein 2) This gene encodes a homolog of Drosophila prickle. The exact function of this gene is not known, however, studies in mice suggest that it may be involved in seizure prevention. Mutations in this gene are associated with progressive myoclonic epilepsy type 5. [provided by RefSeq, Dec 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.1926001).
BS2
?
High AC in GnomAdExome4 at 28 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRICKLE2 | NM_198859.4 | c.454G>A | p.Gly152Ser | missense_variant | 5/8 | ENST00000638394.2 | |
PRICKLE2 | NM_001370528.1 | c.454G>A | p.Gly152Ser | missense_variant | 5/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRICKLE2 | ENST00000638394.2 | c.454G>A | p.Gly152Ser | missense_variant | 5/8 | 1 | NM_198859.4 | ||
PRICKLE2 | ENST00000295902.11 | c.622G>A | p.Gly208Ser | missense_variant | 6/9 | 5 | P1 | ||
PRICKLE2 | ENST00000564377.6 | c.454G>A | p.Gly152Ser | missense_variant | 5/8 | 5 | |||
PRICKLE2 | ENST00000640303.1 | n.1093G>A | non_coding_transcript_exon_variant | 3/6 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152220Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000360 AC: 9AN: 250190Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135456
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GnomAD4 exome AF: 0.0000192 AC: 28AN: 1461710Hom.: 0 Cov.: 34 AF XY: 0.0000165 AC XY: 12AN XY: 727158
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152338Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74508
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Progressive myoclonic epilepsy type 5 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 152 of the PRICKLE2 protein (p.Gly152Ser). This variant is present in population databases (rs199566606, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with PRICKLE2-related conditions. ClinVar contains an entry for this variant (Variation ID: 478007). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PRICKLE2 protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
D;D;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
M;M;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
Polyphen
B;B;.
MVP
0.79
MPC
0.66
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