3-64099131-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_198859.4(PRICKLE2):c.2455C>T(p.Pro819Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,894 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 (★). Synonymous variant affecting the same amino acid position (i.e. P819P) has been classified as Likely benign.
Frequency
Consequence
NM_198859.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRICKLE2 | NM_198859.4 | c.2455C>T | p.Pro819Ser | missense_variant | 8/8 | ENST00000638394.2 | |
PRICKLE2-AS1 | NR_045697.1 | n.2505G>A | non_coding_transcript_exon_variant | 3/3 | |||
PRICKLE2 | NM_001370528.1 | c.2455C>T | p.Pro819Ser | missense_variant | 8/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRICKLE2 | ENST00000638394.2 | c.2455C>T | p.Pro819Ser | missense_variant | 8/8 | 1 | NM_198859.4 | ||
PRICKLE2-AS1 | ENST00000482609.1 | n.2505G>A | non_coding_transcript_exon_variant | 3/3 | 1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461894Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727248
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Progressive myoclonic epilepsy type 5 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 26, 2020 | In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a PRICKLE2-related disease. This sequence change replaces proline with serine at codon 819 of the PRICKLE2 protein (p.Pro819Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at