About TP53
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
TP53 c.845G>A, p.(Arg282Gln)
Classification
Uncertain significance
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is uncertain. Select a step to read what it means.
Uncertain.The recorded classification is uncertain significance.
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 ClinGen TP53 VCEP v2.4.0. 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: 3
Benign evidence criteria: 0
Pathogenic criteria applied · 3
PM1Moderate
PM1 · moderate
This missense variant affects TP53 codon 282, one of the codons explicitly designated by the TP53 VCEP as a mutational hotspot for PM1 at Moderate strength.
PM2Supporting
PM2 · supporting
This variant is rare in population databases. In gnomAD v4.1, the overall allele frequency is 5.58e-06, which is below the TP53 PM2 threshold of 3.0e-05, and the highest observed subpopulation frequency is 2.23e-05, which is below the 4.0e-05 subpopulation threshold. gnomAD v2.1 shows 1 allele among 251444 alleles (3.98e-06).
PP3Supporting
PP3 · supporting
Computational evidence supports a deleterious effect. The TP53 VCEP PP3/BP4 spreadsheet assigns PP3 to c.845G>A; BayesDel is 0.477696, above the TP53 pathogenic threshold of 0.16, REVEL is high at 0.887, and SpliceAI shows no predicted splice effect (max delta score 0.00).
Benign criteria applied · 0
No benign criterion marked as applied in the recorded assessment.
Recorded classification: Uncertain significance
Tavtigian et.al., 2020 - Bayesian adaptation of Richards et.al., 2015 v2.4.0 point-based framework: PM1 moderate (+2) + PM2 supporting (+1) + PP3 supporting (+1) = 4 points, which maps to VUS.
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
9 / 1,613,956 alleles
gnomAD v4.1: 9 / 1,613,956 alleles. Recorded AF 5.57636e-06. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 3.97703e-06; MAF= 0.00040%, 1/251444 alleles, homozygotes = 0) and has highest observed frequency in the European (Finnish) population (AF= 4.61979e-05; MAF= 0.00462%, 1/21646 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
14 reported laboratory submissions
11 Uncertain significance · 2 Likely pathogenic · 1 Uncertain Significance.
Context only
ClinVar ↗
Functional evidence
Statement recorded
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Loss-of-function; curated oncogenicity label: Likely Oncogenic.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
46 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV52689673, n = 46 times).
Cancer Hotspots
This variant lies in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under ClinGen TP53 VCEP v2.4.0, with the data and sources behind each one.
28 criteria with recorded statuses: 3 met · 5 not met · 8 not assessed · 12 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
The TP53 c.845G>A (p.Arg282Gln) variant has been reported in ClinVar with conflicting germline classifications and is also described in somatic cancer literature at a recurrent TP53 hotspot residue.
This variant is rare in population databases, with an allele frequency of 5.58e-06 in gnomAD v4.1 and 3.98e-06 in gnomAD v2.1, which supports PM2 at Supporting strength under the TP53 VCEP thresholds.
Available functional evidence is mixed and does not meet TP53 VCEP criteria for either damaging or benign functional evidence; the TP53 functional worksheet assigns p.Arg282Gln as 'No evidence' for PS3/BS3.
Computational evidence supports a deleterious effect because the TP53 VCEP in silico worksheet assigns PP3 to c.845G>A, BayesDel is 0.477696, REVEL is 0.887, and SpliceAI predicts no meaningful splice impact.
No criteria match.
Met · 3
PM1 ModerateThis missense variant affects TP53 codon 282, one of the codons explicitly designated by the TP53 VCEP as a mutational hotspot for PM1 at Moderate strength. Details ▾Hide ▴
Rule
TP53 PM1_Moderate applies to missense variants at codon 282.
Evidence considered
- TP53 VCEP PM1 codon list includes codon 282
- Published somatic/structural literature describes Arg282 as a TP53 hotspot residue
Sources
PM2 SupportingThis variant is rare in population databases. In gnomAD v4.1, the overall allele frequency is 5.58e-06, which is below the TP53 PM2 threshold of 3.0e-05, and the highest observed subpopulation frequency is 2.23e-05, which is below the 4.0e-05 subpopulation threshold. gnomAD v2.1 shows 1 allele among 251444 alleles (3.98e-06). Details ▾Hide ▴
Rule
TP53 PM2_Supporting applies when AF <0.00003 and no qualifying subpopulation exceeds 0.00004.
Evidence considered
- gnomAD v4.1 AF 5.576e-06
- best subpopulation AF 2.229e-05
- gnomAD v2.1 AF 3.977e-06
Sources
PP3 SupportingComputational evidence supports a deleterious effect. The TP53 VCEP PP3/BP4 spreadsheet assigns PP3 to c.845G>A; BayesDel is 0.477696, above the TP53 pathogenic threshold of 0.16, REVEL is high at 0.887, and SpliceAI shows no predicted splice effect (max delta score 0.00). Details ▾Hide ▴
Rule
For TP53 missense variants, PP3 applies per the TP53 VCEP in silico framework and spreadsheet assignment.
Evidence considered
- VCEP PP3-BP4 table entry: c.845G>A -> PP3
- BayesDel 0.477696
- REVEL 0.887
- SpliceAI max delta 0.00
Sources
cspec ↗vcep_pp3_bp4_codesbayesdelrevelspliceai ↗vcep_flowchart_for_application_of_pp3_2c_bp4_2c_and_bp7
Not met · 5 · evaluated, threshold not reached
PS3 TP53 VCEP functional data do not support PS3 for this variant. The TP53 functional worksheet entry for p.Arg282Gln is assigned 'No evidence', indicating the available assay results do not meet the VCEP threshold for damaging functional evidence. Details ▾Hide ▴
Rule
Apply TP53 PS3 only when functional assay combinations satisfy the VCEP worksheet/flowchart criteria.
Evidence considered
- TP53 functional worksheet row for R282Q is preassigned 'No evidence'
- Published studies describe abnormal or mixed functional findings
- but not a TP53 VCEP PS3-level assignment
Sources
vcep_functional_worksheetvcep_flowchart_for_application_of_functional_rule_codesPMID:11896595 ↗PMID:11920959 ↗PMID:18453682 ↗
BA1 Population frequency does not meet the TP53 BA1 threshold. The highest available filtering allele frequency remains well below 0.001. Details ▾Hide ▴
Rule
TP53 BA1 requires FAF >=0.001 in a qualifying subpopulation.
Evidence considered
- gnomAD frequencies are far below BA1 cutoff
Sources
BS1 Population frequency does not meet the TP53 BS1 threshold. The observed population frequencies are below the TP53 BS1 cutoff of 0.0003. Details ▾Hide ▴
Rule
TP53 BS1 requires qualifying FAF >=0.0003 and <0.001.
Evidence considered
- gnomAD v4.1 best subpopulation AF 2.229e-05
- gnomAD v2.1 best subpopulation AF 4.620e-05
Sources
BS3 TP53 VCEP functional data do not support BS3 for this variant. The TP53 functional worksheet entry for p.Arg282Gln is assigned 'No evidence', so the available assays do not meet the VCEP threshold for benign functional evidence. Details ▾Hide ▴
Rule
Apply TP53 BS3 only when functional assay combinations satisfy the VCEP worksheet/flowchart criteria for retained function.
Evidence considered
- TP53 functional worksheet row for R282Q is preassigned 'No evidence'
- Available assay findings are not sufficient for BS3 under TP53 VCEP rules
Sources
vcep_functional_worksheetvcep_flowchart_for_application_of_functional_rule_codesPMID:11896595 ↗PMID:11920959 ↗
BP4 Computational evidence does not support BP4. The TP53 VCEP PP3/BP4 spreadsheet assigns PP3 rather than BP4 to c.845G>A, and BayesDel is 0.477696, which is above the TP53 pathogenic threshold of 0.16. Details ▾Hide ▴
Rule
BP4 is not met when the TP53 VCEP in silico framework assigns PP3.
Evidence considered
- VCEP PP3-BP4 table entry: c.845G>A -> PP3
- BayesDel 0.477696
- SpliceAI max delta 0.00
Sources
Not assessed · 8 · no assessment recorded
PS1 No verified TP53 VCEP pathogenic or likely pathogenic variant with the same amino acid change was identified for PS1 assessment. Details ▾Hide ▴
Rule
PS1 requires the same amino acid change as an established TP53 VCEP pathogenic or likely pathogenic variant.
Evidence considered
- Current ClinVar record for p.Arg282Gln is conflicting
- No TP53 expert-panel same-amino-acid comparator was confirmed in the reviewed materials
Still missing
- Direct confirmation of any TP53 VCEP-classified same-amino-acid comparator would be needed.
Sources
PS2 No variant-specific confirmed de novo observation with the TP53 point-based requirements was identified. Details ▾Hide ▴
Rule
TP53 PS2 requires variant-specific point-scored de novo evidence.
Evidence considered
- TP53 VCEP uses point-based PS2 scoring
- Reviewed literature referenced de novo TP53 mutations in general but not a usable variant-specific PS2 case for p.Arg282Gln
Still missing
- Variant-specific maternity/paternity-confirmed or assumed de novo case data would be needed.
Sources
PS4 Although PM2_Supporting is met, no variant-specific germline case series with sufficient TP53 PS4 point scoring were identified, so PS4 cannot be assigned. Details ▾Hide ▴
Rule
TP53 PS4 requires 1 to >=8 points from qualifying proband observations.
Evidence considered
- TP53 VCEP requires point-based PS4 scoring after PM2_Supporting is met
- Available materials did not provide usable p.Arg282Gln-specific point totals
Still missing
- Variant-specific proband data with TP53 LFS point totals would be needed.
Sources
PM5 No fully verified same-residue TP53 VCEP pathogenic or likely pathogenic comparator set was established from the reviewed materials, so PM5 was not assigned. Details ▾Hide ▴
Rule
TP53 PM5 requires qualifying same-residue missense comparators previously determined pathogenic or likely pathogenic under TP53 VCEP specifications.
Evidence considered
- TP53 uses classic same-residue missense PM5 logic
- Reviewed materials did not provide a validated comparator set suitable for final PM5 assignment
Still missing
- Direct confirmation of qualifying TP53 VCEP same-residue pathogenic or likely pathogenic comparators would be needed.
Sources
PP1 No variant-specific segregation data with enough informative meioses were identified to support PP1. Details ▾Hide ▴
Rule
TP53 PP1 requires 3-4, 5-6, or >=7 informative meioses depending on strength.
Evidence considered
- TP53 PP1 requires 3 or more informative meioses depending on strength
- No usable p.Arg282Gln-specific segregation count was established
Still missing
- Variant-specific cosegregation data with counted informative meioses would be needed.
Sources
PP4 No low-variant-allele-fraction blood observation or related mosaicism evidence meeting the TP53 PP4 requirements was identified. Details ▾Hide ▴
Rule
TP53 PP4 applies to qualifying low-VAF observations in blood.
Evidence considered
- TP53 PP4 is a mosaicism-focused rule requiring low-VAF observations
Still missing
- Variant-specific blood VAF and supporting constitutional mosaicism evidence would be needed.
Sources
BS2 No single-source dataset showing the required number of unrelated females age 60 years or older without cancer was identified for this variant. Details ▾Hide ▴
Rule
TP53 BS2 requires 2-3, 4-7, or >=8 unrelated unaffected older females from a single source depending on strength.
Evidence considered
- No TP53 BS2-qualifying unaffected cohort was identified
Still missing
- A qualifying unaffected female cohort from one source would be needed.
Sources
BS4 No variant-specific lack-of-segregation data in affected relatives with Li-Fraumeni syndrome-associated cancers were identified. Details ▾Hide ▴
Rule
TP53 BS4 requires lack of segregation in affected family members with LFS-associated cancers.
Evidence considered
- No usable p.Arg282Gln-specific nonsegregation evidence was established
Still missing
- Variant-specific nonsegregation data in affected relatives would be needed.
Sources
Not applicable · 12· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/AThis is a missense variant, not a nonsense, frameshift, canonical splice, or other TP53 null variant, so PVS1 does not apply. Details ▾Hide ▴
Rule
TP53 PVS1 decision tree applies to null/splice classes, not this missense change.
Evidence considered
- TP53 VCEP includes a gene-specific PVS1 framework
- pvs1_variant_assessment classifies this variant outside generic null-variant buckets
Sources
PM3 VCEPPM3 is not used in the TP53 VCEP framework. Details ▾Hide ▴
VCEP rule
Not applicable for TP53 VCEP.
Evidence considered
- TP53 VCEP marks PM3 as not applicable
Sources
PM4 VCEPPM4 is not used in the TP53 VCEP framework. Details ▾Hide ▴
VCEP rule
Not applicable for TP53 VCEP.
Evidence considered
- TP53 VCEP marks PM4 as not applicable
Sources
PM6 VCEPPM6 is not used in the TP53 VCEP framework. Details ▾Hide ▴
VCEP rule
Not applicable for TP53 VCEP.
Evidence considered
- TP53 VCEP marks PM6 as not applicable
Sources
PP2 VCEPPP2 is not used in the TP53 VCEP framework. Details ▾Hide ▴
VCEP rule
Not applicable for TP53 VCEP.
Evidence considered
- TP53 VCEP marks PP2 as not applicable
Sources
PP5 VCEPPP5 is not used in the TP53 VCEP framework. Details ▾Hide ▴
VCEP rule
Not applicable for TP53 VCEP.
Evidence considered
- TP53 VCEP marks PP5 as not applicable
Sources
BP1 VCEPBP1 is not used in the TP53 VCEP framework. Details ▾Hide ▴
VCEP rule
Not applicable for TP53 VCEP.
Evidence considered
- TP53 VCEP marks BP1 as not applicable
Sources
BP2 VCEPBP2 is not used in the TP53 VCEP framework. Details ▾Hide ▴
VCEP rule
Not applicable for TP53 VCEP.
Evidence considered
- TP53 VCEP marks BP2 as not applicable
Sources
BP3 VCEPBP3 is not used in the TP53 VCEP framework. Details ▾Hide ▴
VCEP rule
Not applicable for TP53 VCEP.
Evidence considered
- TP53 VCEP marks BP3 as not applicable
Sources
BP5 VCEPBP5 is not used in the TP53 VCEP framework. Details ▾Hide ▴
VCEP rule
Not applicable for TP53 VCEP.
Evidence considered
- TP53 VCEP marks BP5 as not applicable
Sources
BP6 VCEPBP6 is not used in the TP53 VCEP framework. Details ▾Hide ▴
VCEP rule
Not applicable for TP53 VCEP.
Evidence considered
- TP53 VCEP marks BP6 as not applicable
Sources
BP7 N/ABP7 does not apply because this is a missense variant rather than a synonymous or qualifying intronic variant. Details ▾Hide ▴
Rule
TP53 BP7 applies only to synonymous or qualifying intronic variants.
Evidence considered
- TP53 BP7 framework is limited to synonymous/intronic variants
Sources
cspec ↗vcep_flowchart_for_application_of_pp3_2c_bp4_2c_and_bp7
Identifiers
- Gene
- TP53
- Transcript
- NM_000546.6
- Coding (HGVS c.)
- NM_000546.6:c.845G>A
- Protein (HGVS p.)
- NP_000537.3:p.(Arg282Gln)
- GRCh38
- chr17:7673775 C>T
- GRCh37
- chr17:7577093 C>T
- ClinVar
- 237956
- COSMIC
- COSV52689673
Gene diagram
Every interpreted variant in TP53, mapped onto the exon structure of NM_000546.6. Select a row to find it on the plot.
TP53NM_000546.6
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 TP53
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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
9 / 1,613,956 alleles
AF 5.58e-06 · 0 homozygotes · FAF 1.83e-06
gnomAD v2.1
1 / 251,444 alleles
AF 3.98e-06 · 0 homozygotes
By genetic ancestry
gnomAD v4.1
AF 5.6e-06 · 9 / 1,613,956 alleles · 0 hom · FAF 1.8e-06
| East Asian1 / 44,858 | 2.2e-05 |
| European (Finnish)1 / 64,030 | 1.6e-05 |
| African/African American1 / 74,898 | 1.3e-05 |
| European (non-Finnish)6 / 1,180,030 | 5.1e-06 |
0 alternate alleles recorded in 6 other groups: Remaining individuals, Admixed American, Amish, Middle Eastern, South Asian, Ashkenazi Jewish.
gnomAD v2.1
AF 4e-06 · 1 / 251,444 alleles · 0 hom
| European (Finnish)1 / 21,646 | 4.6e-05 |
0 alternate alleles recorded in 7 other groups: African/African American, Admixed American, Ashkenazi Jewish, East Asian, European (non-Finnish), Remaining individuals, South Asian.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 5.57636e-06; MAF= 0.00056%, 9/1613956 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 2.22926e-05; MAF= 0.00223%, 1/44858 alleles, homozygotes = 0); grpmax FAF= 1.83e-06.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 3.97703e-06; MAF= 0.00040%, 1/251444 alleles, homozygotes = 0) and has highest observed frequency in the European (Finnish) population (AF= 4.61979e-05; MAF= 0.00462%, 1/21646 alleles, homozygotes = 0).
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.887
- BayesDel
- 0.478
How the predictions were used
PP3 SupportingComputational evidence supports a deleterious effect. The TP53 VCEP PP3/BP4 spreadsheet assigns PP3 to c.845G>A; BayesDel is 0.477696, above the TP53 pathogenic threshold of 0.16, REVEL is high at 0.887, and SpliceAI shows no predicted splice effect (max delta score 0.00). Details ▾Hide ▴
Rule
For TP53 missense variants, PP3 applies per the TP53 VCEP in silico framework and spreadsheet assignment.
Evidence considered
- VCEP PP3-BP4 table entry: c.845G>A -> PP3
- BayesDel 0.477696
- REVEL 0.887
- SpliceAI max delta 0.00
Sources
cspec ↗vcep_pp3_bp4_codesbayesdelrevelspliceai ↗vcep_flowchart_for_application_of_pp3_2c_bp4_2c_and_bp7
BP4 Computational evidence does not support BP4. The TP53 VCEP PP3/BP4 spreadsheet assigns PP3 rather than BP4 to c.845G>A, and BayesDel is 0.477696, which is above the TP53 pathogenic threshold of 0.16. Details ▾Hide ▴
Rule
BP4 is not met when the TP53 VCEP in silico framework assigns PP3.
Evidence considered
- VCEP PP3-BP4 table entry: c.845G>A -> PP3
- BayesDel 0.477696
- SpliceAI max delta 0.00
Sources
BP7 N/ABP7 does not apply because this is a missense variant rather than a synonymous or qualifying intronic variant. Details ▾Hide ▴
Rule
TP53 BP7 applies only to synonymous or qualifying intronic variants.
Evidence considered
- TP53 BP7 framework is limited to synonymous/intronic variants
Sources
cspec ↗vcep_flowchart_for_application_of_pp3_2c_bp4_2c_and_bp7
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.887. BayesDel score = 0.477696.
8 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 18453682 ↗Impact of low-frequency hotspot mutation R282Q on the structure of p53 DNA-binding domain as revealed by crystallography at 1.54 angstroms resolution.No paper-specific finding is recorded.
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PMID 26619011 ↗Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.No paper-specific finding is recorded.
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PMID 10864200 ↗P53 germline mutations in childhood cancers and cancer risk for carrier individuals.Chompret A et al. · 2000No paper-specific finding is recorded.
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PMID 11429705 ↗p53 mutants can often transactivate promoters containing a p21 but not Bax or PIG3 responsive elements.No paper-specific finding is recorded.
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PMID 11782540 ↗A peptide that binds and stabilizes p53 core domain: chaperone strategy for rescue of oncogenic mutants.No paper-specific finding is recorded.
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PMID 11896595 ↗Tumour p53 mutations exhibit promoter selective dominance over wild type p53.Monti P et al. · 2002No paper-specific finding is recorded.
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PMID 11920959 ↗Complex functions of mutant p53 alleles from human prostate cancer.Shi XB et al. · 2002No paper-specific finding is recorded.
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PMID 28492532 ↗Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.No paper-specific finding is recorded.
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
9 / 1,613,956 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
11 Uncertain significance · 2 Likely pathogenic · 1 Uncertain Significance
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 ↗
ClinGen CSpec
Captured ClinGen CSpec source record
Open source ↗
All source links
- ClinGen CSpec ↗cspec.genome.network/cspec/ui/svi/doc/135637581
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/237956/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/17-7577093-C-T?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr17-7673775-C-T?dataset=gnomad_r4
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000546.6%3Ac.845G…
- OncoKB ↗www.oncokb.org/gene/TP53/R282Q
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=121498690
- 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= 5.57636e-06; MAF= 0.00056%, 9/1613956 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 2.22926e-05; MAF= 0.00223%, 1/44858 alleles, homozygotes = 0); grpmax FAF= 1.83e-06.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 3.97703e-06; MAF= 0.00040%, 1/251444 alleles, homozygotes = 0) and has highest observed frequency in the European (Finnish) population (AF= 4.61979e-05; MAF= 0.00462%, 1/21646 alleles, homozygotes = 0).
ClinVar
This variant has been reported in ClinVar as Uncertain significance (11 clinical laboratories) and as Likely pathogenic (2 clinical laboratories) and as Uncertain Significance (1 clinical laboratory). (ClinVarID = 237956)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.887. BayesDel score = 0.477696.
Functional
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Loss-of-function; curated oncogenicity label: Likely Oncogenic.
Somatic
This variant lies in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV52689673, n = 46 times).
Cancer Hotspots
This variant lies in a statistically significant hotspot.