About PRKN
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
PRKN c.1204C>T, p.(Arg402Cys)
Classification
Likely benign
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is likely benign. Select a step to read what it means.
Likely benign.A likely benign classification under the recorded framework.
In plain language
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.
LYFE Sciences is an AI system, and it can make mistakes.
Criteria may be applied incorrectly, sources may be misread, and a
confident-looking classification can still be wrong.
Double-check every criterion and its underlying evidence
before relying on any call.
01The reasoning
How it was classified
The recorded framework is Not recorded. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.
Recorded applied criteria
The applied criteria and their strengths are shown as assessed under the stated framework.
Pathogenic evidence criteria: 0
Benign evidence criteria: 2
Pathogenic criteria applied · 0
No pathogenic criterion marked as applied in the recorded assessment.
Benign criteria applied · 2
BS2Strong
BS2 · strong
This variant has been observed in the homozygous state in population databases: 4 homozygotes in gnomAD v2.1 and 12 homozygotes in gnomAD v4.1. For autosomal recessive early-onset Parkinson disease (ARJP) caused by biallelic PRKN pathogenic variants, the presence of multiple homozygous individuals in general population databases constitutes strong evidence for a benign classification.
BP4Supporting
BP4 · supporting
Multiple lines of computational evidence suggest no impact on the gene product. BayesDel score 0.144 is in the clearly benign range. SpliceAI predicts no splicing impact (max delta = 0.0). REVEL score 0.627 is in the indeterminate zone but does not reach a pathogenic threshold. Preponderance of in silico evidence supports a benign interpretation.
Recorded classification: Likely benign
gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: BS2 strong benign, BP4 supporting benign; combination = 1 strong benign + 1 supporting benign, which maps to Likely Benign.
02The sources
Evidence at a glance
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1
gnomAD v2.1
Population frequency
2,996 / 1,614,156 alleles
gnomAD v4.1: 2,996 / 1,614,156 alleles. Recorded AF 0.00185608. Recorded homozygote count 12.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.00186997; MAF= 0.18700%, 529/282892 alleles, homozygotes = 4) and has highest observed frequency in the European (Finnish) population (AF= 0.00338322; MAF= 0.33832%, 85/25124 alleles, homozygotes = 0); grpmax FAF= 0.00214045.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.0020086862106406082, 37/18420 alleles, homozygotes = 0).
SpliceAI score
0.000 maximum delta
Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
4 reported laboratory submissions
2 Likely benign · 1 Uncertain significance · 1 Benign. ClinVar API review status: criteria provided, conflicting classifications.
Context only
ClinVar ↗
Functional evidence
Statement recorded
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. PRKN encodes a tumor suppressor invovled in tagging cellular proteins for degradation. PRKN is inactivated in various cancer types, and its dysfunctio
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
3 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV58208986, n = 3 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under Not recorded, with the data and sources behind each one.
26 criteria with recorded statuses: 2 met · 21 not met · 0 not assessed · 3 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
This variant has been observed in the homozygous state in population databases (4 homozygotes in gnomAD v2.1, 12 homozygotes in gnomAD v4.1), meeting BS2 (strong benign) for an autosomal recessive early-onset Parkinson disease with full penetrance.
Multiple lines of computational evidence suggest no deleterious impact: BayesDel score 0.144 is in the benign range, SpliceAI predicts no splicing effect (max delta 0.0), and REVEL score 0.627 is indeterminate. Meeting BP4 at supporting benign level.
Combination of BS2 (strong benign) and BP4 (supporting benign) meets the generic ACMG/AMP 2015 threshold for Likely Benign (1 Strong benign + 1 Supporting benign).
No criteria match.
Met · 2
BS2 StrongThis variant has been observed in the homozygous state in population databases: 4 homozygotes in gnomAD v2.1 and 12 homozygotes in gnomAD v4.1. For autosomal recessive early-onset Parkinson disease (ARJP) caused by biallelic PRKN pathogenic variants, the presence of multiple homozygous individuals in general population databases constitutes strong evidence for a benign classification. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: 4 homozygotes (529/282892 alleles
- AF=0.187%). gnomAD v4.1: 12 homozygotes (2996/1614156 alleles
- AF=0.186%). Multiple homozygotes in population databases for a fully penetrant recessive disorder indicate the variant is likely benign.
Sources
BP4 SupportingMultiple lines of computational evidence suggest no impact on the gene product. BayesDel score 0.144 is in the clearly benign range. SpliceAI predicts no splicing impact (max delta = 0.0). REVEL score 0.627 is in the indeterminate zone but does not reach a pathogenic threshold. Preponderance of in silico evidence supports a benign interpretation. Details ▾Hide ▴
Evidence considered
- BayesDel=0.144 (benign range)
- SpliceAI max delta=0.0 (no splicing impact)
- REVEL=0.627 (indeterminate). Two of three predictors support benign
- combined evidence meets BP4 at supporting level.
Sources
Not met · 21 · evaluated, threshold not reached
PS1 No evidence of a different nucleotide change at c.1204 resulting in the same amino acid change (p.Arg402Cys) that has been independently classified as pathogenic. Details ▾Hide ▴
Evidence considered
- No alternate nucleotide change at this position yielding p.Arg402Cys identified in ClinVar or literature.
PS2 No de novo observation reported for this variant. No publications or ClinVar submissions provide de novo evidence. Details ▾Hide ▴
Evidence considered
- PMID:23279440 (EFNS PD diagnostic guidelines) does not contain variant-specific data
- no de novo observations identified in any source.
Sources
PS3 No variant-specific functional studies identified. OncoKB reports Unknown Oncogenic Effect with no curated functional evidence for this variant. No publications with functional data were retrieved. Details ▾Hide ▴
Evidence considered
- OncoKB: Unknown Oncogenic Effect
- no variant-specific functional evidence. No experimental functional studies in literature.
Still missing
- No functional assays performed on p.Arg402Cys or a systematically characterized range that includes residue 402.
Sources
PS4 No case-control or enrichment data demonstrating increased prevalence of this variant in affected individuals versus controls. The variant has an overall allele frequency of 0.187% in gnomAD v2.1, which is inconsistent with a rare pathogenic variant for autosomal recessive early-onset Parkinson disease. Screen_PS4 passed zero publications. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: AF=0.187% overall
- 4 homozygotes. PS4 screening returned zero qualifying observations.
Sources
PM1 Residue Arg402 is not located in a statistically significant mutational hotspot per cancerhotspots.org. No ClinGen-specified critical functional domain data available for PRKN residue 402 in the case materials. Details ▾Hide ▴
Evidence considered
- Cancerhotspots.org: no significant hotspot at R402. No domain-level specification available.
PM2 Variant allele frequency in gnomAD v2.1 is 0.187% (529/282892 alleles), which exceeds the 0.1% threshold for PM2 under generic ACMG framework. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 AF=0.187% (529/282892 alleles
- 4 homozygotes)
- gnomAD v4.1 AF=0.186% (2996/1614156 alleles
- 12 homozygotes)
- exceeds PM2 <0.1% cutoff.
Sources
PM5 No same-residue comparator variants identified. PM5 candidate harvesting returned zero candidates; unable to confirm classic same-residue PM5 semantics. Details ▾Hide ▴
Evidence considered
- PM5 candidate search returned zero comparator variants at residue Arg402.
Sources
pm5_candidates
PM6 No de novo observation reported. No publications or clinical submissions document a confirmed de novo event for this variant. Details ▾Hide ▴
Evidence considered
- No de novo data in any source.
PP1 No segregation data available. No family studies demonstrating cosegregation of c.1204C>T with disease phenotype. Details ▾Hide ▴
Evidence considered
- PMID:24816432 describes SYNJ1 p.Arg258Gln segregation
- not PRKN c.1204C>T. No variant-specific segregation data identified.
Sources
PP2 PRKN missense variants can be pathogenic (loss-of-function) via the ubiquitin-proteasome pathway, and this variant has high population frequency with multiple homozygotes, indicating the gene tolerates benign missense variation. Both criteria for PP2 (low rate of benign missense AND missense as common disease mechanism) are not jointly satisfied for this gene. Details ▾Hide ▴
Evidence considered
- PRKN has both pathogenic and benign missense variants. The gene does not meet the low-rate-of-benign-missense requirement.
Sources
PP3 Multiple lines of computational evidence do not support a deleterious effect. REVEL score 0.627 is in the indeterminate range (above 0.5 but below typical pathogenic thresholds of 0.7-0.75). BayesDel 0.144 is in the benign range. SpliceAI delta 0.0 predicts no splicing impact. In silico tools are discordant and do not collectively support pathogenicity. Details ▾Hide ▴
Evidence considered
- REVEL=0.627 (indeterminate)
- BayesDel=0.144 (benign)
- SpliceAI max delta=0.0 (no splicing impact). Discordant and insufficient for PP3.
Sources
PP4 No patient phenotype data available to assess whether the individual's clinical presentation is highly specific for PRKN-related disease. Details ▾Hide ▴
Evidence considered
- No patient phenotype information provided.
Still missing
- Patient phenotype data required for PP4 assessment.
PP5 ClinVar classification is Likely benign (2 clinical laboratories), Benign (1), and Uncertain significance (1), with 1-star review status ('criteria provided, conflicting classifications'). Under the user-specified framework, PP5 requires ClinVar 3-star expert panel review. ClinVar Variation ID 425402 has only 1-star status and conflicting classifications. Details ▾Hide ▴
Evidence considered
- ClinVar 425402: 1-star review status
- conflicting classifications
- does not meet PP5 3-star EP requirement.
Sources
BA1 Overall allele frequency in gnomAD v2.1 is 0.187%, which is below the 1% threshold for BA1 under generic ACMG framework. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 AF=0.187% (529/282892 alleles)
- gnomAD v4.1 AF=0.186% (2996/1614156 alleles). Does not exceed BA1 >1% cutoff.
Sources
BS1 Overall allele frequency in gnomAD v2.1 is 0.187% (grpmax FAF 0.214%), which is below the 0.3% threshold for BS1 under generic ACMG framework. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 AF=0.187%
- grpmax FAF=0.214%
- gnomAD v4.1 AF=0.186%
- grpmax FAF=0.259%. Does not exceed BS1 >0.3% cutoff.
Sources
BS3 No in vitro or in vivo functional studies demonstrating no damaging effect on protein function or splicing were identified for this variant. Details ▾Hide ▴
Evidence considered
- No functional studies showing benign effect identified.
Still missing
- No experimental data characterizing the functional impact of p.Arg402Cys.
BS4 No segregation data demonstrating lack of cosegregation with disease. The only segregation-themed publication (PMID:24816432) describes SYNJ1 mutation segregation, not PRKN. Details ▾Hide ▴
Evidence considered
- PMID:24816432 pertains to SYNJ1 p.Arg258Gln
- a different gene. No PRKN c.1204C>T segregation data available.
Still missing
- No PRKN-specific segregation data available.
Sources
BP2 No evidence of this variant observed in trans with a known dominant pathogenic variant. No allelic phase data available. Details ▾Hide ▴
Evidence considered
- No trans configuration data available for BP2 assessment.
Still missing
- Phase information with dominant pathogenic variants not available.
BP5 No evidence of an alternate molecular basis for disease in a case harboring this variant. No clinical case data with alternative diagnoses available. Details ▾Hide ▴
Evidence considered
- No alternate molecular basis data available.
Still missing
- Patient-level clinical data with alternative molecular diagnoses not available.
BP6 ClinVar classification for this variant is Likely benign (2 labs) / Benign (1 lab) / VUS (1 lab) with 1-star review status ('criteria provided, conflicting classifications'). Under the user-specified framework, BP6 requires ClinVar 3-star expert panel review. ClinVar Variation ID 425402 has only 1-star status and conflicting classifications; it does not meet the 3-star EP requirement. Details ▾Hide ▴
Evidence considered
- ClinVar 425402: 1-star review status with conflicting classifications (Likely benign/Benign/VUS). Does not meet BP6 3-star EP requirement.
Sources
PS5 No evidence of a second pathogenic variant in trans identified for this recessive disorder. No patient-level genotype data available to assess allelic configuration. Details ▾Hide ▴
Evidence considered
- No trans configuration data available.
Not applicable · 3· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/AMissense variant (c.1204C>T, p.Arg402Cys) does not fall into PVS1 null-variant buckets (nonsense, frameshift, canonical ±1,2 splice consensus). Generic PVS1 framework not applicable per pvs1_variant_assessment.json. Details ▾Hide ▴
Evidence considered
- Variant is a missense substitution
- not a null variant eligible for PVS1.
Sources
pvs1_variant_assessmentpvs1_gene_context
BP1 N/APRKN pathogenic variants include both missense and truncating changes; the gene is not one in which only truncating variants cause disease. Details ▾Hide ▴
Evidence considered
- PRKN loss-of-function mechanism encompasses both missense and truncating pathogenic variants
- BP1 does not apply.
Sources
pvs1_gene_context
BP7 N/Ac.1204C>T is a missense variant (p.Arg402Cys), not a synonymous/silent variant. BP7 applies only to synonymous variants with no predicted splice impact. Details ▾Hide ▴
Evidence considered
- Variant is missense
- not synonymous
- BP7 does not apply.
Identifiers
- Gene
- PRKN
- Transcript
- NM_004562.2
- Coding (HGVS c.)
- NM_004562.2:c.1204C>T
- Protein (HGVS p.)
- NP_004553.2:p.(Arg402Cys)
- GRCh38
- chr6:161360169 G>A
- GRCh37
- chr6:161781201 G>A
- ClinVar
- 425402
- COSMIC
- COSV58208986
Gene diagram
Every interpreted variant in PRKN, mapped onto the exon structure of NM_004562.2. Select a row to find it on the plot.
PRKNNM_004562.2
Fetching transcript structure from UCSC…
Exons
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Transcript span
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Strand
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Variants mapped
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Source
UCSC ncbiRefSeqCurated
All variants in PRKN
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Select a row to find it on the plot; use the link to open its page.
| Protein | Location | Classification | Link |
|---|
gnomAD v4.1
2,996 / 1,614,156 alleles
AF 0.00186 · 12 homozygotes · FAF 0.00259
gnomAD v2.1
529 / 282,892 alleles
AF 0.00187 · 4 homozygotes · FAF 0.00214
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 0.0019 · 2996 / 1,614,156 alleles · 12 hom · FAF 0.0026
| Middle Eastern23 / 6,060 | 0.00381 hom |
| European (Finnish)197 / 64,036 | 0.0031 |
| South Asian187 / 91,086 | 0.00214 hom |
| Admixed American121 / 60,032 | 0.002 |
| European (non-Finnish)2286 / 1,180,002 | 0.00197 hom |
| Remaining individuals111 / 62,506 | 0.0018 |
| African/African American67 / 75,044 | 0.00089 |
| Ashkenazi Jewish3 / 29,606 | 0.0001 |
| East Asian1 / 44,874 | 2.2e-05 |
0 alternate alleles recorded in 1 other group: Amish.
gnomAD v2.1
AF 0.0019 · 529 / 282,892 alleles · 4 hom · FAF 0.0021
| European (Finnish)85 / 25,124 | 0.0034 |
| Remaining individuals17 / 7,226 | 0.0024 |
| European (non-Finnish)290 / 129,198 | 0.00222 hom |
| South Asian58 / 30,616 | 0.00192 hom |
| Admixed American52 / 35,440 | 0.0015 |
| African/African American27 / 24,966 | 0.0011 |
0 alternate alleles recorded in 2 other groups: Ashkenazi Jewish, East Asian.
gnomAD-Canada
AF not recorded · ? / ? alleles
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 0.00185608; MAF= 0.18561%, 2996/1614156 alleles, homozygotes = 12) and has highest observed frequency in the Middle Eastern population (AF= 0.00379538; MAF= 0.37954%, 23/6060 alleles, homozygotes = 1); grpmax FAF= 0.00259375.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.00186997; MAF= 0.18700%, 529/282892 alleles, homozygotes = 4) and has highest observed frequency in the European (Finnish) population (AF= 0.00338322; MAF= 0.33832%, 85/25124 alleles, homozygotes = 0); grpmax FAF= 0.00214045.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.0020086862106406082, 37/18420 alleles, homozygotes = 0).
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.627
- BayesDel
- 0.144
How the predictions were used
BP4 SupportingMultiple lines of computational evidence suggest no impact on the gene product. BayesDel score 0.144 is in the clearly benign range. SpliceAI predicts no splicing impact (max delta = 0.0). REVEL score 0.627 is in the indeterminate zone but does not reach a pathogenic threshold. Preponderance of in silico evidence supports a benign interpretation. Details ▾Hide ▴
Evidence considered
- BayesDel=0.144 (benign range)
- SpliceAI max delta=0.0 (no splicing impact)
- REVEL=0.627 (indeterminate). Two of three predictors support benign
- combined evidence meets BP4 at supporting level.
Sources
PP3 Multiple lines of computational evidence do not support a deleterious effect. REVEL score 0.627 is in the indeterminate range (above 0.5 but below typical pathogenic thresholds of 0.7-0.75). BayesDel 0.144 is in the benign range. SpliceAI delta 0.0 predicts no splicing impact. In silico tools are discordant and do not collectively support pathogenicity. Details ▾Hide ▴
Evidence considered
- REVEL=0.627 (indeterminate)
- BayesDel=0.144 (benign)
- SpliceAI max delta=0.0 (no splicing impact). Discordant and insufficient for PP3.
Sources
BP7 N/Ac.1204C>T is a missense variant (p.Arg402Cys), not a synonymous/silent variant. BP7 applies only to synonymous variants with no predicted splice impact. Details ▾Hide ▴
Evidence considered
- Variant is missense
- not synonymous
- BP7 does not apply.
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.627. BayesDel score = 0.143758.
5 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata. None of the listed paper records explicitly indicates that the variant is named.
Recorded publications
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PMID 23279440 ↗EFNS/MDS-ES/ENS [corrected] recommendations for the diagnosis of Parkinson's disease.Berardelli A et al. · 2013EFNS/MDS-ES/ENS consensus recommendations for the diagnosis of Parkinson disease. Discusses diagnostic criteria, genetic testing recommendations, and differential diagnosis at the guideline level. NM_004562.2(PRKN):c.1204C>T was not identified in this paper.Does not name this variant
Quoted passage
Genetic testing for specific mutations is recommended on an individual basis (Level B), taking into account specific features (i.e. family history and age of onset).
Abstract reviewed; full-text not available
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PMID 24816432 ↗PARK20 caused by SYNJ1 homozygous Arg258Gln mutation in a new Italian family.Olgiati S et al. · 2014Reports a homozygous SYNJ1 c.773G>A (p.Arg258Gln) mutation in two siblings with early-onset atypical parkinsonism (PARK20). This paper concerns the SYNJ1 gene, not PRKN. NM_004562.2(PRKN):c.1204C>T was not identified in this paper.Does not name this variant
Quoted passage
SYNJ1 has been recently identified by two independent groups as the gene defective in a novel form of autosomal recessive, early-onset atypical parkinsonism (PARK20).
Abstract reviewed; full-text not available
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PMID 20301402 ↗Monogenic Parkinson Disease Overview.Adam MP et al. · 1993Monogenic Parkinson Disease Overview — a GeneReviews clinical summary covering multiple monogenic Parkinson disease genes. No abstract or full-text available for review. NM_004562.2(PRKN):c.1204C>T was not confirmed in available content.Does not name this variant
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PMID 20301651 ↗PRKN-Related Early-Onset Parkinson Disease.Adam MP et al. · 1993PRKN-Related Early-Onset Parkinson Disease — a GeneReviews clinical summary of PRKN-associated Parkinson disease. No abstract or full-text available for review. NM_004562.2(PRKN):c.1204C>T was not confirmed in available content.Does not name this variant
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PMID 28492532 ↗Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.Nykamp K et al. · 2017Describes the Sherloc refinement of the ACMG-AMP variant classification framework. A methodological paper that does not report on any specific variant. NM_004562.2(PRKN):c.1204C>T was not identified in this paper.Does not name this variant
Quoted passage
We undertook an iterative process of refining the ACMG-AMP guidelines. We used the guidelines to classify more than 40,000 clinically observed variants, assessed the outcome, and refined the classification criteria to capture exceptions and edge cases.
Abstract reviewed; full-text not available
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
2,996 / 1,614,156 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.000
Open source ↗
ClinVar
2 Likely benign · 1 Uncertain significance · 1 Benign
Open source ↗
COSMIC
Captured COSMIC source record
Open source ↗
Cancer hotspots
Captured Cancer Hotspots source record
Open source ↗
OncoKB
Captured OncoKB source record
Open source ↗
All source links
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/425402/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/6-161781201-G-A?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr6-161360169-G-A?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/6-161360169-G-A
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_004562.2%3Ac.1204…
- OncoKB ↗www.oncokb.org/gene/PRKN/R402C
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=133346845
- Cancer hotspots ↗www.cancerhotspots.org/
Statements for reports
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 0.00185608; MAF= 0.18561%, 2996/1614156 alleles, homozygotes = 12) and has highest observed frequency in the Middle Eastern population (AF= 0.00379538; MAF= 0.37954%, 23/6060 alleles, homozygotes = 1); grpmax FAF= 0.00259375.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.00186997; MAF= 0.18700%, 529/282892 alleles, homozygotes = 4) and has highest observed frequency in the European (Finnish) population (AF= 0.00338322; MAF= 0.33832%, 85/25124 alleles, homozygotes = 0); grpmax FAF= 0.00214045.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.0020086862106406082, 37/18420 alleles, homozygotes = 0).
ClinVar
This variant has been reported in ClinVar as Likely benign (2 clinical laboratories) and as Uncertain significance (1 clinical laboratory) and as Benign (1 clinical laboratory). (ClinVarID = 425402)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.627. BayesDel score = 0.143758.
Functional
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. PRKN encodes a tumor suppressor invovled in tagging cellular proteins for degradation. PRKN is inactivated in various cancer types, and its dysfunctio
Somatic
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV58208986, n = 3 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.