chr3-64099773-C-A
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP5BP4BS2
The NM_198859.4(PRICKLE2):c.1813G>T(p.Val605Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,614,116 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_198859.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PRICKLE2 | NM_198859.4 | c.1813G>T | p.Val605Phe | missense_variant | Exon 8 of 8 | ENST00000638394.2 | NP_942559.1 | |
PRICKLE2 | NM_001370528.1 | c.1813G>T | p.Val605Phe | missense_variant | Exon 8 of 8 | NP_001357457.1 | ||
PRICKLE2-AS1 | NR_045697.1 | n.3147C>A | non_coding_transcript_exon_variant | Exon 3 of 3 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152222Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251414Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135876
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461894Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 727248
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152222Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74370
ClinVar
Submissions by phenotype
Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Pathogenic:1
This variant has been previously reported as disease-causing and was found once in our laboratory maternally inherited in a 2-year-old female with speech delay, regression, hypoglycemia, abnormal MRI, possible seizures -
not specified Uncertain:1
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not provided Uncertain:1
The PRICKLE2 c.1813G>T (p.Val605Phe) variant has been observed in two patients with myoclonic epilepsy, developmental regression and episodes concerning seizures (Tao H et al., PMID: 21276947; Yang Y et al., PMID: 25326635). This variant is only observed on 3/251,414 alleles in the general population (gnomAD v.2.1.1), indicating it is not a common variant. Computational predictors are uncertain as to the impact of this variant on PRICKLE2 function. This variant has been reported in the ClinVar database as a germline variant of uncertain significance by two submitters and pathogenic by one submitter in an individual with speech delay, regression, hypoglycemia, abnormal brain MRI, and possible seizures. Due to limited information, the clinical significance of this variant is uncertain. -
Progressive myoclonic epilepsy type 5 Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at