About RUNX1
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
RUNX1 c.590G>A, p.(Arg197Gln)
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 RUNX1 VCEP v3.1.0. 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: 2
Benign evidence criteria: 0
Pathogenic criteria applied · 2
PM1Supporting
PM1 · supporting
This missense variant affects Arg197, which lies within the RUNX1 Runt homology domain residue range 89-204 defined by the RUNX1 VCEP for PM1_Supporting. The residue is within the critical DNA-binding domain but is not one of the 13 residues specified for PM1_Strong.
PM2Supporting
PM2 · supporting
This variant is present at very low frequency in population databases. In gnomAD v4.1, the grpmax FAF is 6.8e-07, which is below the RUNX1 PM2_Supporting threshold of 5.0e-05, with 4/1611650 alleles observed overall and more than 2000 alleles assessed; gnomAD v2.1 likewise shows only 1/250946 alleles.
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 v3.1.0 point-based framework: PM1 supporting (+1) + PM2 supporting (+1) = 2 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
4 / 1,611,650 alleles
gnomAD v4.1: 4 / 1,611,650 alleles. Recorded AF 2.48193e-06. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 3.98492e-06; MAF= 0.00040%, 1/250946 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 8.81368e-06; MAF= 0.00088%, 1/113460 alleles, homozygotes = 0).
SpliceAI score
0.010 maximum delta
Recorded SpliceAI maximum delta score: 0.010. Refer to the recorded PP3/BP4 rationale for interpretation.
No listed criterion applied
SpliceAI ↗
ClinVar submissions
3 reported laboratory submissions
3 Uncertain significance.
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. RUNX1, a transcription factor involved in hematopoietic differentiation, is altered by mutation or chromosomal rearrangement in various hematologic ma
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
No matching record reported
This variant has not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under ClinGen RUNX1 VCEP v3.1.0, with the data and sources behind each one.
28 criteria with recorded statuses: 2 met · 7 not met · 8 not assessed · 11 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
The RUNX1 c.590G>A (p.Arg197Gln) variant has not been observed in somatic cancers in COSMIC and has been reported in ClinVar as Uncertain Significance, including an expert-panel submission from the ClinGen Myeloid Malignancy VCEP.
This variant is present at very low frequency in population databases, with gnomAD v4.1 showing 4/1611650 alleles and a grpmax FAF of 6.8e-07, which is below the RUNX1 PM2_Supporting threshold of 5.0e-05.
No reviewed variant-specific functional evidence demonstrating either abnormal or normal RUNX1 function was identified, so the current evidence does not support PS3 or BS3.
This missense change affects Arg197 within the RUNX1 Runt homology domain, supporting PM1_Supporting under the RUNX1 VCEP, but computational evidence does not meet PP3 or BP4 because REVEL is 0.702, SpliceAI is 0.01, and the RUNX1 thresholds are REVEL at least 0.88 for PP3 and less than 0.50 with SpliceAI at most 0.20 for BP4.
No criteria match.
Met · 2
PM1 SupportingThis missense variant affects Arg197, which lies within the RUNX1 Runt homology domain residue range 89-204 defined by the RUNX1 VCEP for PM1_Supporting. The residue is within the critical DNA-binding domain but is not one of the 13 residues specified for PM1_Strong. Details ▾Hide ▴
Rule
PM1_Supporting for missense variants affecting other amino acid residues 89-204 within the RHD; PM1_Strong reserved for 13 specified residues.
Evidence considered
- Protein consequence p.(Arg197Gln)
- RUNX1 VCEP PM1 rule for residues 89-204
- pilot VCEP precedent showing PM1 use within this domain.
Sources
cspec ↗vcep_myeloid_malignancy_vcep_runx1_pilot_results
PM2 SupportingThis variant is present at very low frequency in population databases. In gnomAD v4.1, the grpmax FAF is 6.8e-07, which is below the RUNX1 PM2_Supporting threshold of 5.0e-05, with 4/1611650 alleles observed overall and more than 2000 alleles assessed; gnomAD v2.1 likewise shows only 1/250946 alleles. Details ▾Hide ▴
Rule
RUNX1 PM2_Supporting requires minor allele frequency <=0.00005 with adequate allele count and coverage.
Evidence considered
- gnomAD v4.1 grpmax FAF 6.8e-07 and total AF 2.48e-06
- gnomAD v2.1 total AF 3.98e-06
- RUNX1 PM2_Supporting threshold <=0.00005.
Sources
Not met · 7 · evaluated, threshold not reached
PVS1 This variant is a missense substitution, not a predicted loss-of-function variant, and available evidence does not indicate a canonical splice-site or other null effect that would support PVS1. Details ▾Hide ▴
Rule
RUNX1 VCEP PVS1 applies to loss-of-function variant classes; this missense variant does not meet that rule.
Evidence considered
- Protein consequence p.(Arg197Gln)
- RUNX1 VCEP PVS1 framework
- generic PVS1 scaffold does not place this variant in a null-variant category.
Sources
PS1 No previously established pathogenic or likely pathogenic variant causing the same amino acid change was identified in the reviewed ClinVar evidence, so PS1 is not met. Details ▾Hide ▴
PM5 No different missense variant at the same residue was verified as pathogenic or likely pathogenic in the reviewed evidence, so PM5 is not met. Details ▾Hide ▴
Rule
RUNX1 PM5 requires a different pathogenic or likely pathogenic missense change at the same amino acid residue, with additional VCEP caveats.
Evidence considered
- ClinVar same-residue review did not identify a qualifying pathogenic or likely pathogenic missense comparator
- RUNX1 VCEP PM5 rule.
Sources
PP3 Available computational evidence does not meet the RUNX1 PP3 threshold. REVEL is 0.702, which is below the PP3 cutoff of 0.88, and SpliceAI max delta score is 0.01, which is below the splice threshold of 0.38. BayesDel is 0.137586, but the RUNX1 VCEP computational rule is based on REVEL and SpliceAI. Details ▾Hide ▴
Rule
RUNX1 PP3 for missense variants requires REVEL >=0.88 or SpliceAI >=0.38.
Evidence considered
- REVEL 0.702
- SpliceAI max delta 0.01
- BayesDel 0.137586
- RUNX1 PP3 thresholds.
Sources
BA1 Population frequency is far below the RUNX1 BA1 threshold. In gnomAD v4.1, total AF is 2.48e-06 and grpmax FAF is 6.8e-07, both below the BA1 threshold of 0.0015. Details ▾Hide ▴
Rule
RUNX1 BA1 requires minor allele frequency >=0.0015 in a qualifying general population dataset.
Evidence considered
- gnomAD v4.1 total AF 2.48e-06 and grpmax FAF 6.8e-07
- RUNX1 BA1 threshold 0.0015.
Sources
BS1 Population frequency does not reach the RUNX1 BS1 range. The highest observed gnomAD v4.1 population AF is 2.23264e-05 in East Asian samples, which is below the BS1 lower threshold of 0.00015. Details ▾Hide ▴
Rule
RUNX1 BS1 requires allele frequency between 0.00015 and 0.0015 in a qualifying population dataset.
Evidence considered
- gnomAD v4.1 highest subpopulation AF 2.23264e-05
- RUNX1 BS1 lower threshold 0.00015.
Sources
BP4 Available computational evidence does not meet the RUNX1 BP4 rule. Although SpliceAI is 0.01 and is below the benign splice cutoff of 0.20, REVEL is 0.702 and is not below the BP4 missense cutoff of 0.50. Details ▾Hide ▴
Rule
RUNX1 BP4 for missense variants requires REVEL <0.50 and SpliceAI <=0.20.
Evidence considered
- REVEL 0.702
- SpliceAI max delta 0.01
- BayesDel 0.137586
- RUNX1 BP4 thresholds.
Sources
Not assessed · 8 · no assessment recorded
PS2 No confirmed de novo occurrence with maternity and paternity established was identified for this variant. Details ▾Hide ▴
Rule
PS2_Supporting requires 1 proven de novo case and PS2_Moderate requires at least 2 proven de novo cases in RUNX1-related disease.
Evidence considered
- RUNX1 VCEP PS2 thresholds
- ClinVar record without qualifying de novo evidence.
Still missing
- Published or curated case-level parental confirmation data were not identified.
Sources
PS3 No validated variant-specific functional assay showing abnormal RUNX1 activity was identified, so PS3 cannot be applied from the current evidence. Details ▾Hide ▴
Rule
RUNX1 PS3 requires altered transactivation with additional functional support, or qualifying alternative functional evidence per VCEP thresholds.
Evidence considered
- RUNX1 VCEP PS3 rule
- OncoKB page did not provide reviewed variant-specific functional evidence.
Still missing
- Direct transactivation or secondary assay data for p.(Arg197Gln) were not identified.
Sources
PS4 This variant has been reported in ClinVar, but no verified count of unrelated probands meeting RUNX1 phenotypic criteria was identified to support PS4. Details ▾Hide ▴
Rule
RUNX1 PS4 requires at least 1 qualifying proband for PS4_Supporting, 2-3 for PS4_Moderate, or at least 4 for PS4.
Evidence considered
- RUNX1 VCEP PS4 thresholds
- ClinVar record shows submission presence but not qualifying proband counts.
Still missing
- Case-level proband counts and phenotype confirmation were not identified.
Sources
PM6 No assumed de novo occurrences without full parental confirmation were identified for this variant. Details ▾Hide ▴
Rule
RUNX1 PM6_Supporting requires 2-3 assumed de novo cases and PM6 requires at least 4 assumed de novo cases.
Evidence considered
- RUNX1 VCEP PM6 thresholds
- ClinVar record without qualifying assumed de novo evidence.
Still missing
- Case-level inheritance data were not identified.
Sources
PP1 No segregation data were identified for this variant, so PP1 cannot be applied. Details ▾Hide ▴
BS3 No validated variant-specific functional study showing normal RUNX1 function was identified, so BS3 cannot be applied. Details ▾Hide ▴
Rule
RUNX1 BS3 requires normal transactivation with or without qualifying secondary evidence depending on strength.
Evidence considered
- RUNX1 VCEP BS3 rule
- no reviewed variant-specific normal-function evidence identified.
Still missing
- Direct transactivation or secondary normal-function assay data for p.(Arg197Gln) were not identified.
Sources
BS4 No convincing non-segregation data were identified for this variant. Details ▾Hide ▴
BP2 No evidence was identified that this variant is in trans with a pathogenic RUNX1 variant or in cis with a pathogenic variant, so BP2 cannot be applied. Details ▾Hide ▴
Rule
Observed in trans with a pathogenic variant for a fully penetrant dominant disorder, or observed in cis with a pathogenic variant.
Evidence considered
- RUNX1 VCEP BP2 rule
- no qualifying co-occurrence evidence identified.
Still missing
- Phase data and co-occurrence data were not identified.
Sources
Not applicable · 11· recorded as not applicable Show reasons ▾Hide reasons ▴
PM3 VCEPPM3 is not applicable in the RUNX1 germline dominant framework used for this variant. Details ▾Hide ▴
VCEP rule
Criterion marked not applicable by the RUNX1 VCEP.
Evidence considered
- RUNX1 VCEP applicability table.
Sources
PM4 N/AThis variant is a missense substitution and not an in-frame insertion/deletion or stop-loss variant, so PM4 does not apply. Details ▾Hide ▴
Rule
RUNX1 PM4 is restricted to in-frame indels and stop-loss variants.
Evidence considered
- RUNX1 VCEP PM4 rule applies to in-frame indels and stop-loss variants.
Sources
PP2 VCEPPP2 is not applicable in the RUNX1 VCEP framework. Details ▾Hide ▴
VCEP rule
Criterion marked not applicable by the RUNX1 VCEP.
Evidence considered
- RUNX1 VCEP applicability table.
Sources
PP4 VCEPPP4 is not applicable in the RUNX1 VCEP framework because the associated phenotype is not considered sufficiently specific for this rule. Details ▾Hide ▴
VCEP rule
Criterion marked not applicable by the RUNX1 VCEP.
Evidence considered
- RUNX1 VCEP applicability statement for PP4.
Sources
PP5 VCEPPP5 is not used in this framework. Details ▾Hide ▴
VCEP rule
Criterion marked not applicable by the VCEP and SVI recommendations.
Evidence considered
- RUNX1 VCEP applicability statement for PP5.
Sources
BS2 VCEPBS2 is not applicable in the RUNX1 VCEP framework. Details ▾Hide ▴
VCEP rule
Criterion marked not applicable by the RUNX1 VCEP.
Evidence considered
- RUNX1 VCEP applicability table.
Sources
BP1 VCEPBP1 is not applicable in the RUNX1 VCEP framework. Details ▾Hide ▴
VCEP rule
Criterion marked not applicable by the RUNX1 VCEP.
Evidence considered
- RUNX1 VCEP applicability table.
Sources
BP3 VCEPBP3 is not applicable in the RUNX1 VCEP framework. Details ▾Hide ▴
VCEP rule
Criterion marked not applicable by the RUNX1 VCEP.
Evidence considered
- RUNX1 VCEP applicability table.
Sources
BP5 VCEPBP5 is not applicable in the RUNX1 VCEP framework. Details ▾Hide ▴
VCEP rule
Criterion marked not applicable by the RUNX1 VCEP.
Evidence considered
- RUNX1 VCEP applicability table.
Sources
BP6 VCEPBP6 is not used in this framework. Details ▾Hide ▴
VCEP rule
Criterion marked not applicable by the VCEP and SVI recommendations.
Evidence considered
- RUNX1 VCEP applicability statement for BP6.
Sources
BP7 N/AThis variant is missense rather than synonymous or intronic, so BP7 does not apply. Details ▾Hide ▴
Rule
RUNX1 BP7 applies to qualifying synonymous or intronic variants with low splice prediction scores.
Evidence considered
- Variant consequence p.(Arg197Gln)
- RUNX1 BP7 rule limited to synonymous and intronic variants.
Sources
Identifiers
- Gene
- RUNX1
- Transcript
- NM_001001890.2
- Coding (HGVS c.)
- NM_001001890.2:c.590G>A
- Protein (HGVS p.)
- NP_001001890.1:p.(Arg197Gln)
- GRCh38
- chr21:34834544 C>T
- GRCh37
- chr21:36206841 C>T
- ClinVar
- 580214
Gene diagram
Every interpreted variant in RUNX1, mapped onto the exon structure of NM_001001890.2. Select a row to find it on the plot.
RUNX1NM_001001890.2
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 RUNX1
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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
4 / 1,611,650 alleles
AF 2.48e-06 · 0 homozygotes · FAF 6.8e-07
gnomAD v2.1
1 / 250,946 alleles
AF 3.98e-06 · 0 homozygotes
By genetic ancestry
gnomAD v4.1
AF 2.5e-06 · 4 / 1,611,650 alleles · 0 hom · FAF 6.8e-07
| East Asian1 / 44,790 | 2.2e-05 |
| European (non-Finnish)3 / 1,179,746 | 2.5e-06 |
0 alternate alleles recorded in 8 other groups: Remaining individuals, Admixed American, European (Finnish), Amish, Middle Eastern, South Asian, Ashkenazi Jewish, African/African American.
gnomAD v2.1
AF 4e-06 · 1 / 250,946 alleles · 0 hom
| European (non-Finnish)1 / 113,460 | 8.8e-06 |
0 alternate alleles recorded in 7 other groups: African/African American, Admixed American, Ashkenazi Jewish, East Asian, European (Finnish), Remaining individuals, South Asian.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 2.48193e-06; MAF= 0.00025%, 4/1611650 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 2.23264e-05; MAF= 0.00223%, 1/44790 alleles, homozygotes = 0); grpmax FAF= 6.8e-07.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 3.98492e-06; MAF= 0.00040%, 1/250946 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 8.81368e-06; MAF= 0.00088%, 1/113460 alleles, homozygotes = 0).
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.702
- BayesDel
- 0.138
How the predictions were used
PP3 Available computational evidence does not meet the RUNX1 PP3 threshold. REVEL is 0.702, which is below the PP3 cutoff of 0.88, and SpliceAI max delta score is 0.01, which is below the splice threshold of 0.38. BayesDel is 0.137586, but the RUNX1 VCEP computational rule is based on REVEL and SpliceAI. Details ▾Hide ▴
Rule
RUNX1 PP3 for missense variants requires REVEL >=0.88 or SpliceAI >=0.38.
Evidence considered
- REVEL 0.702
- SpliceAI max delta 0.01
- BayesDel 0.137586
- RUNX1 PP3 thresholds.
Sources
BP4 Available computational evidence does not meet the RUNX1 BP4 rule. Although SpliceAI is 0.01 and is below the benign splice cutoff of 0.20, REVEL is 0.702 and is not below the BP4 missense cutoff of 0.50. Details ▾Hide ▴
Rule
RUNX1 BP4 for missense variants requires REVEL <0.50 and SpliceAI <=0.20.
Evidence considered
- REVEL 0.702
- SpliceAI max delta 0.01
- BayesDel 0.137586
- RUNX1 BP4 thresholds.
Sources
BP7 N/AThis variant is missense rather than synonymous or intronic, so BP7 does not apply. Details ▾Hide ▴
Rule
RUNX1 BP7 applies to qualifying synonymous or intronic variants with low splice prediction scores.
Evidence considered
- Variant consequence p.(Arg197Gln)
- RUNX1 BP7 rule limited to synonymous and intronic variants.
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01). REVEL score = 0.702. BayesDel score = 0.137586.
14 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 22138009 ↗NCCN Task Force report: Evaluating the clinical utility of tumor markers in oncology.No paper-specific finding is recorded.
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PMID 23619275 ↗ACMG position statement on prenatal/preconception expanded carrier screening.No paper-specific finding is recorded.
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PMID 23652378 ↗A framework to start the debate on neonatal screening policies in the EU: an Expert Opinion Document.Cornel MC et al. · 2014No paper-specific finding is recorded.
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PMID 25626707 ↗Whole-genome sequencing in newborn screening? A statement on the continued importance of targeted approaches in newborn screening programmes.Howard HC et al. · 2015No paper-specific finding is recorded.
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PMID 25730230 ↗Expanded carrier screening in reproductive medicine-points to consider: a joint statement of the American College of Medical Genetics and Genomics, American College of Obstetricians and Gynecologists, National Society of Genetic Counselors, Perinatal Quality Foundation, and Society for Maternal-Fetal Medicine.Edwards JG et al. · 2015No paper-specific finding is recorded.
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PMID 25741868 ↗Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.No paper-specific finding is recorded.
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PMID 20963938 ↗PMID:20963938No paper-specific finding is recorded.
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PMID 23169492 ↗The perspective from EASAC and FEAM on direct-to-consumer genetic testing for health-related purposes.Fears R et al. · 2013No paper-specific finding is recorded.
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PMID 22947299 ↗Specific guidelines for assessing and improving the methodological quality of economic evaluations of newborn screening.Langer A et al. · 2012No paper-specific finding is recorded.
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PMID 23037933 ↗Including the initial newborn screening bloodspot collection device serial number on birth certificates: basis and recommendations from the Secretary of Health and Human Services' Advisory Committee on Heritable Disorders in Newborns and Children.Therrell BL et al. · 2013No paper-specific finding is recorded.
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PMID 23881473 ↗Newborn screening: education, consent, and the residual blood spot. The position of the national society of genetic counselors.Blout C et al. · 2014No paper-specific finding is recorded.
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PMID 24022298 ↗Offering prenatal diagnostic tests: European guidelines for clinical practice [corrected].Skirton H et al. · 2014No paper-specific finding is recorded.
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PMID 24394680 ↗Parental permission for pilot newborn screening research: guidelines from the NBSTRN.Botkin JR et al. · 2014No 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
4 / 1,611,650 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.010
Open source ↗
ClinVar
3 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/135637580
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/580214/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/21-36206841-C-T?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr21-34834544-C-T?dataset=gn…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_001001890.2%3Ac.5…
- OncoKB ↗www.oncokb.org/gene/RUNX1/R197Q
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=RUNX1+c.590G%3EA
- 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= 2.48193e-06; MAF= 0.00025%, 4/1611650 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 2.23264e-05; MAF= 0.00223%, 1/44790 alleles, homozygotes = 0); grpmax FAF= 6.8e-07.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 3.98492e-06; MAF= 0.00040%, 1/250946 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 8.81368e-06; MAF= 0.00088%, 1/113460 alleles, homozygotes = 0).
ClinVar
This variant has been reported in ClinVar as Uncertain significance (3 clinical laboratories) and as Uncertain Significance by ClinGen Myeloid Malignancy Variant Curation Expert Panel (expert panel). (ClinVarID = 580214)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01). REVEL score = 0.702. BayesDel score = 0.137586.
Functional
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. RUNX1, a transcription factor involved in hematopoietic differentiation, is altered by mutation or chromosomal rearrangement in various hematologic ma
Somatic
This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.