rs27673
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_198859.4(PRICKLE2):āc.816T>Cā(p.Asp272=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.995 in 1,613,902 control chromosomes in the GnomAD database, including 799,631 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.99 ( 74145 hom., cov: 33)
Exomes š: 1.0 ( 725486 hom. )
Consequence
PRICKLE2
NM_198859.4 synonymous
NM_198859.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.979
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=-0.93).
BP6
?
Variant 3-64147674-A-G is Benign according to our data. Variant chr3-64147674-A-G is described in ClinVar as [Benign]. Clinvar id is 130137.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-64147674-A-G is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-0.979 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.991 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRICKLE2 | NM_198859.4 | c.816T>C | p.Asp272= | synonymous_variant | 7/8 | ENST00000638394.2 | |
PRICKLE2 | NM_001370528.1 | c.816T>C | p.Asp272= | synonymous_variant | 7/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRICKLE2 | ENST00000638394.2 | c.816T>C | p.Asp272= | synonymous_variant | 7/8 | 1 | NM_198859.4 |
Frequencies
GnomAD3 genomes ? AF: 0.986 AC: 150138AN: 152202Hom.: 74089 Cov.: 33
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GnomAD3 exomes AF: 0.995 AC: 246851AN: 248062Hom.: 122840 AF XY: 0.996 AC XY: 133908AN XY: 134434
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GnomAD4 exome AF: 0.996 AC: 1456230AN: 1461582Hom.: 725486 Cov.: 61 AF XY: 0.997 AC XY: 724608AN XY: 727106
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GnomAD4 genome ? AF: 0.986 AC: 150253AN: 152320Hom.: 74145 Cov.: 33 AF XY: 0.987 AC XY: 73487AN XY: 74480
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ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Progressive myoclonic epilepsy type 5 Benign:3
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | Nov 11, 2016 | - - |
not specified Benign:2
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | - | Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 20, 2018 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | May 03, 2018 | - - |
Progressive myoclonic epilepsy Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
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