rs144455095
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_198859.4(PRICKLE2):c.1527G>A(p.Glu509=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00039 in 1,614,016 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0022 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00020 ( 0 hom. )
Consequence
PRICKLE2
NM_198859.4 synonymous
NM_198859.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.358
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 Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
Variant 3-64146963-C-T is Benign according to our data. Variant chr3-64146963-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 448121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.358 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00219 (334/152214) while in subpopulation AFR AF= 0.00672 (279/41514). AF 95% confidence interval is 0.00607. There are 1 homozygotes in gnomad4. There are 170 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 334 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRICKLE2 | NM_198859.4 | c.1527G>A | p.Glu509= | synonymous_variant | 7/8 | ENST00000638394.2 | |
PRICKLE2 | NM_001370528.1 | c.1527G>A | p.Glu509= | synonymous_variant | 7/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRICKLE2 | ENST00000638394.2 | c.1527G>A | p.Glu509= | synonymous_variant | 7/8 | 1 | NM_198859.4 |
Frequencies
GnomAD3 genomes AF: 0.00219 AC: 333AN: 152096Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000644 AC: 162AN: 251378Hom.: 0 AF XY: 0.000523 AC XY: 71AN XY: 135850
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GnomAD4 exome AF: 0.000202 AC: 295AN: 1461802Hom.: 0 Cov.: 34 AF XY: 0.000172 AC XY: 125AN XY: 727190
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GnomAD4 genome AF: 0.00219 AC: 334AN: 152214Hom.: 1 Cov.: 32 AF XY: 0.00228 AC XY: 170AN XY: 74442
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Aug 22, 2016 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2022 | PRICKLE2: BP4, BS1 - |
PRICKLE2-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 05, 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). - |
Progressive myoclonic epilepsy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Progressive myoclonic epilepsy type 5 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 21, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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