About RUNX1
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
RUNX1 c.624C>T, p.(Ala208=)
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: 1
Benign evidence criteria: 3
Pathogenic criteria applied · 1
PM2Supporting
PM2 · supporting
PM2_Supporting is met under the MM-VCEP specification. The grpmax filtering allele frequency (FAF) in gnomAD v4.1 is 3.259e-05 (0.00326%), which is below the VCEP threshold of ≤0.00005 (0.005%). The variant is present in ≥2,000 alleles tested (1,613,324 total alleles).
Benign criteria applied · 3
BP4Supporting
BP4 · supporting
BP4 is met under the MM-VCEP specification for synonymous variants. The VCEP rule for synonymous variants requires SpliceAI ≤0.20. SpliceAI predicts no significant splice impact (max delta score = 0.02), which is well below the 0.20 threshold. Multiple lines of computational evidence suggest no impact on splicing.
BP6Supporting
BP6 · supporting
Expert panel ClinGen Myeloid Malignancy Variant Curation Expert Panel classified as Likely benign.
BP7Supporting
BP7 · supporting
BP7 is met under the MM-VCEP specification. The variant is a synonymous change (c.624C>T, p.Ala208=) located in exon 4, not within the last 3 nucleotides preceding the canonical donor splice site (c.722-724) or the first nucleotide following the canonical acceptor splice site (c.533). SpliceAI predicts no splice impact (max delta = 0.02 ≤ 0.20). Conservation data is no longer required per the VCEP v3.1.0 update.
Recorded classification: Uncertain significance
Tavtigian et.al., 2020 - Bayesian adaptation of Richards et.al., 2015 v3.1.0 point-based framework: PM2 supporting (+1) = 1 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
53 / 1,613,324 alleles
gnomAD v4.1: 53 / 1,613,324 alleles. Recorded AF 3.28514e-05. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 7.08275e-06; MAF= 0.00071%, 2/282376 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 1.55072e-05; MAF= 0.00155%, 2/128972 alleles, homozygotes = 0).
SpliceAI score
0.020 maximum delta
Recorded SpliceAI maximum delta score: 0.020. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
2 reported laboratory submissions
2 Likely benign.
Functional evidence
Statement recorded
OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.
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.
26 criteria with recorded statuses: 4 met · 11 not met · 1 not assessed · 10 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_001001890.2:c.624C>T (p.Ala208=) is a synonymous variant in exon 4 of RUNX1 that does not alter the amino acid sequence.
This variant is present at extremely low frequency in gnomAD (v4.1 grpmax FAF = 3.259e-05, 53/1,613,324 alleles), meeting PM2_Supporting under the MM-VCEP specification (MAF ≤0.00005).
SpliceAI predicts no splice impact (max delta = 0.02), meeting BP4 (SpliceAI ≤0.20 for synonymous variants) under the MM-VCEP specification.
The variant meets BP7 as a synonymous change not located in the critical splice region (not in the last 3 nucleotides of exon 4 nor the first nucleotide after the acceptor site), with SpliceAI ≤0.20.
The ClinGen Myeloid Malignancy VCEP classified this variant as Likely Benign (ClinVar ID 532686, SCV001366061, reviewed by expert panel), consistent with the computed Tavtigian score of -1 (PM2_Supporting +1, BP4 -1, BP7 -1).
No pathogenic evidence was identified: no de novo occurrences (PS2/PM6), no probands with FPD/AML phenotype (PS4), no functional data demonstrating damaging effect (PS3), no cosegregation data (PP1), the variant lies outside the RHD (PM1 not met), and in silico predictions do not support pathogenicity (PP3 not met).
Population frequencies are too low to meet BA1 (>0.15%) or BS1 (0.015%-0.15%), but the variant is not absent from population databases.
BS3 could not be independently assessed as the primary functional assay data reviewed by the expert panel is not publicly accessible through ClinVar; however, the expert panel's Likely Benign classification implies functional evidence was not supportive of pathogenicity.
No criteria match.
Met · 4
PM2 SupportingPM2_Supporting is met under the MM-VCEP specification. The grpmax filtering allele frequency (FAF) in gnomAD v4.1 is 3.259e-05 (0.00326%), which is below the VCEP threshold of ≤0.00005 (0.005%). The variant is present in ≥2,000 alleles tested (1,613,324 total alleles). Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 grpmax FAF = 3.259e-05 ≤ 0.00005
- 1
- 613
- 324 alleles tested
- ≥2
- 000 minimum met
Still missing
- Coverage depth at the position in gnomAD v4.1 not explicitly verified
- assumed ≥20x per VCEP caveat
Sources
BP4 SupportingBP4 is met under the MM-VCEP specification for synonymous variants. The VCEP rule for synonymous variants requires SpliceAI ≤0.20. SpliceAI predicts no significant splice impact (max delta score = 0.02), which is well below the 0.20 threshold. Multiple lines of computational evidence suggest no impact on splicing. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.02 ≤ 0.20 (BP4 threshold for synonymous variants)
Sources
BP6 SupportingExpert panel ClinGen Myeloid Malignancy Variant Curation Expert Panel classified as Likely benign. Details ▾Hide ▴
BP7 SupportingBP7 is met under the MM-VCEP specification. The variant is a synonymous change (c.624C>T, p.Ala208=) located in exon 4, not within the last 3 nucleotides preceding the canonical donor splice site (c.722-724) or the first nucleotide following the canonical acceptor splice site (c.533). SpliceAI predicts no splice impact (max delta = 0.02 ≤ 0.20). Conservation data is no longer required per the VCEP v3.1.0 update. Details ▾Hide ▴
Evidence considered
- Synonymous variant not in critical splice region (not in last 3 nt of exon 4
- not first nt after acceptor)
- SpliceAI max delta = 0.02 ≤ 0.20
Sources
Not met · 11 · evaluated, threshold not reached
PS2 No proven de novo occurrences (with both maternity and paternity confirmed) of c.624C>T have been reported in patients with FPD/AML phenotype. The variant is observed in population databases at low frequency, consistent with inherited rather than de novo origin. Details ▾Hide ▴
Evidence considered
- No de novo reports identified in ClinVar or literature
- Variant present in gnomAD v4.1 at low frequency (AF=3.29e-05)
- indicating inheritance rather than de novo origin
Sources
PS3 No well-established functional studies demonstrate a damaging effect for this variant. The ClinGen Myeloid Malignancy VCEP classified this variant as Likely Benign, which is inconsistent with PS3-level functional evidence of damage. No independently verifiable functional assay data showing altered transactivation or splicing for c.624C>T was identified. Details ▾Hide ▴
Evidence considered
- ClinGen MM-VCEP expert panel classification of Likely Benign (SCV001366061) implies functional data did not support pathogenicity
- No published functional studies showing damaging effect identified
Still missing
- Direct functional assay data for this specific variant not publicly accessible
- expert panel reviewed data is referenced but not independently verifiable
Sources
PS4 PS4 requires ≥4 probands meeting RUNX1-phenotypic criteria (OR 127.1) for Strong, 2-3 probands for Moderate, or 1 proband for Supporting. No probands with FPD/AML phenotype carrying c.624C>T have been reported in the literature or ClinVar submissions. The variant is observed in gnomAD at low frequency in presumably healthy population controls. Details ▾Hide ▴
Evidence considered
- No probands with FPD/AML phenotype reported
- Variant observed in gnomAD population controls (v2.1: 2/282
- 376
- v4.1: 53/1
- 613
- 324)
Sources
PM1 PM1 requires the variant to affect a residue within the Runt homology domain (RHD, AA 89-204). The variant is a synonymous change at codon 208 (Ala208=), which lies outside the RHD. Additionally, the variant does not alter the amino acid, so no residue is affected. PM1_strong applies only to 13 specific residues (R107, K110, A134, R162, R166, S167, R169, G170, K194, T196, D198, R201, R204), none of which are at position 208. Details ▾Hide ▴
Evidence considered
- Synonymous variant at codon 208
- outside RHD (AA 89-204)
- Position 208 is not among the 13 hotspot residues specified for PM1_strong
Sources
PM6 PM6 requires ≥2 assumed de novo occurrences (PM6_Supporting) or ≥4 (PM6) in patients with FPD/AML phenotype, without confirmation of maternity and paternity. No assumed de novo occurrences of c.624C>T have been reported in the literature or ClinVar. The variant is observed in gnomAD population databases at low frequency, consistent with inherited transmission rather than de novo origin. Details ▾Hide ▴
Evidence considered
- No de novo reports identified
- Variant present in gnomAD
- inconsistent with recurrent de novo origin
Sources
PP1 PP1 requires ≥3 meioses (Supporting), 5-6 meioses (Moderate), or ≥7 meioses (Strong) of cosegregation with disease in affected families. No cosegregation data for c.624C>T with FPD/AML has been reported. The variant's presence in population databases at low frequency is not consistent with strong cosegregation with a rare autosomal dominant disorder. Details ▾Hide ▴
Evidence considered
- No family studies or cosegregation data reported
- Population frequency (v4.1 AF=3.29e-05) not consistent with high-penetrance dominant disorder cosegregation
Still missing
- No familial segregation studies available
Sources
PP3 PP3 for synonymous variants under the MM-VCEP requires SpliceAI ≥0.38, including the creation of cryptic novel splice sites. SpliceAI predicts no significant splice impact for this variant (max delta score = 0.02), which is far below the 0.38 threshold. REVEL score is not available for this variant. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.02
- below PP3 threshold of 0.38
- REVEL score not available
Sources
BA1 BA1 under the MM-VCEP specification requires a minor allele frequency ≥0.0015 (0.15%) in any general continental population dataset with ≥2,000 alleles tested and ≥5 variant alleles. The highest subpopulation frequency is in European (non-Finnish) at 0.00424% (gnomAD v4.1, 50/1,179,988 alleles), which is far below the 0.15% threshold. The gnomAD v2.1 NFE frequency is 0.00155%, also below 0.15%. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 NFE MAF = 0.00424% < 0.15% (BA1 threshold)
- gnomAD v2.1 NFE MAF = 0.00155% < 0.15%
- 5 alleles present in NFE subpopulation (50 in v4.1
- ≥5 minimum met)
Sources
BS1 BS1 under the MM-VCEP specification requires a minor allele frequency between 0.00015 (0.015%) and 0.0015 (0.15%) in any general continental population dataset with ≥2,000 alleles tested and ≥5 variant alleles. The highest subpopulation frequency is in European (non-Finnish) at 0.00424% (gnomAD v4.1), which is below the lower bound of 0.015%. The variant is too rare in all populations to meet BS1. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 NFE MAF = 0.00424% < 0.015% (BS1 lower bound)
- gnomAD v2.1 NFE MAF = 0.00155% < 0.015%
- Variant frequency is too low in all subpopulations for BS1
Sources
BS4 BS4 under the MM-VCEP specification requires observation in ≥2 informative meioses (genotype-negative, phenotype-positive family members). No such segregation data has been reported for c.624C>T. gnomAD reports 0 homozygotes for this variant across all datasets (v2.1 and v4.1), so homozygous observation in healthy individuals cannot support BS4. Details ▾Hide ▴
Evidence considered
- No genotype-negative/phenotype-positive family members reported
- gnomAD reports 0 homozygotes across all datasets
Still missing
- No familial segregation data available to evaluate BS4
Sources
BP2 BP2 requires observation of the variant in trans with a known pathogenic variant in an individual without FPD/AML phenotype, or in cis with a pathogenic variant. No such observations have been reported. gnomAD shows 0 homozygotes across all datasets, so homozygous state evidence is unavailable. Details ▾Hide ▴
Evidence considered
- No reports of c.624C>T in trans with a pathogenic RUNX1 variant
- gnomAD reports 0 homozygotes across v2.1 and v4.1
Still missing
- No compound heterozygote or trans-phase data available
Sources
Not assessed · 1 · no assessment recorded
BS3 BS3 requires well-established functional studies (transactivation assays) showing no damaging effect. The ClinGen MM-VCEP classified this variant as Likely Benign, which implies functional data was reviewed and found to be non-damaging. However, the underlying functional assay data is not publicly accessible through the ClinVar submission record (SCV001366061, no validated PMIDs), and no independently verifiable published functional studies of c.624C>T were identified. BS3 cannot be independently adjudicated without access to the primary functional data reviewed by the expert panel. Details ▾Hide ▴
Evidence considered
- ClinGen MM-VCEP classified as Likely Benign
- implying functional data reviewed
- No independently verifiable published functional studies of this variant identified
Still missing
- Primary functional assay data not publicly accessible
- expert panel's underlying evidence for BS3 is unavailable for independent verification
Sources
Not applicable · 10· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/APVS1 is applicable only to null variants (nonsense, frameshift, canonical ±1,2 splice sites, initiation codon, exon deletion). NM_001001890.2:c.624C>T is a synonymous variant (p.Ala208=) that does not alter the amino acid sequence or create a null allele. Details ▾Hide ▴
Evidence considered
- Synonymous variant
- no null effect on protein
PS1 N/APS1 requires the same amino acid change as a previously established pathogenic variant. This is a synonymous variant that does not produce any amino acid change; there is no amino acid substitution to compare. Details ▾Hide ▴
Evidence considered
- Synonymous variant
- no amino acid change
PM5 N/APM5 requires a missense change at an amino acid residue where a different pathogenic missense change has been observed. This is a synonymous variant that does not alter the amino acid; there is no missense comparator to evaluate. PM5 is not applicable to synonymous variants. Details ▾Hide ▴
Evidence considered
- Synonymous variant
- no amino acid change — cannot evaluate residue-level missense comparators
PP2 VCEPPP2 is not applicable per the MM-VCEP. The RUNX1 missense constraint z-score (2.08-2.48) does not meet the SVI-recommended threshold of ≥3.09. Additionally, nine benign/likely benign missense variants exist in ClinVar for RUNX1. Furthermore, this variant is synonymous rather than missense. Details ▾Hide ▴
Evidence considered
- RUNX1 missense constraint z-score (2.08-2.48) below SVI threshold of 3.09
- Variant is synonymous
- not missense
Sources
PP4 VCEPPP4 is not applicable per the MM-VCEP. The FPD/AML phenotype is rather unspecific and can be caused by other inherited predisposition syndromes, somatic mutations, or environmental factors, insufficient to meet the original ACMG/AMP PP4 rule. Details ▾Hide ▴
Evidence considered
- VCEP specification deems PP4 not applicable for RUNX1 due to unspecific FPD/AML phenotype
Sources
PP5 VCEPPP5 is not for use under this VCEP as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Details ▾Hide ▴
BS2 VCEPBS2 is not applicable per the MM-VCEP. FPD/AML patients display incomplete penetrance and the average age of onset of hematologic malignancies is 33 years, so observation in a healthy adult does not reliably exclude pathogenicity. Details ▾Hide ▴
Evidence considered
- VCEP deems BS2 not applicable due to incomplete penetrance and late age of onset in FPD/AML
Sources
BP1 VCEPBP1 is not applicable per the MM-VCEP. Both truncating and missense variants in RUNX1 cause FPD/AML, so a missense variant cannot be considered benign solely because truncating variants are the primary mechanism. Details ▾Hide ▴
Evidence considered
- VCEP deems BP1 not applicable — both truncating and missense variants cause FPD/AML
Sources
BP5 VCEPBP5 is not applicable per the MM-VCEP. In rare circumstances, a patient can carry two pathogenic variants in genes predisposing to hematologic malignancies, so finding an alternate molecular basis does not reliably exclude RUNX1 pathogenicity. Details ▾Hide ▴
Evidence considered
- VCEP deems BP5 not applicable — patients may carry two pathogenic variants in hematologic malignancy predisposition genes
Sources
PS5 N/APP5 is not for use under this VCEP as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Details ▾Hide ▴
Identifiers
- Gene
- RUNX1
- Transcript
- NM_001001890.2
- Coding (HGVS c.)
- NM_001001890.2:c.624C>T
- Protein (HGVS p.)
- NP_001001890.1:p.(Ala208=)
- GRCh38
- chr21:34834510 G>A
- GRCh37
- chr21:36206807 G>A
- ClinVar
- 532686
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
53 / 1,613,324 alleles
AF 3.29e-05 · 0 homozygotes · FAF 3.26e-05
gnomAD v2.1
2 / 282,376 alleles
AF 7.08e-06 · 0 homozygotes
gnomAD-Canada v1.0
0 / 0 alleles
AF 0 · 0 homozygotes · FAF 0
By genetic ancestry
gnomAD v4.1
AF 3.3e-05 · 53 / 1,613,324 alleles · 0 hom · FAF 3.3e-05
| European (non-Finnish)50 / 1,179,988 | 4.2e-05 |
| Remaining individuals2 / 62,456 | 3.2e-05 |
| South Asian1 / 91,060 | 1.1e-05 |
0 alternate alleles recorded in 7 other groups: Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, Ashkenazi Jewish, African/African American.
gnomAD v2.1
AF 7.1e-06 · 2 / 282,376 alleles · 0 hom
| European (non-Finnish)2 / 128,972 | 1.6e-05 |
0 alternate alleles recorded in 7 other groups: African/African American, Admixed American, Ashkenazi Jewish, East Asian, European (Finnish), Remaining individuals, South Asian.
gnomAD-Canada
AF 0 · 0 / 0 alleles · 0 hom
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 3.28514e-05; MAF= 0.00329%, 53/1613324 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 4.23733e-05; MAF= 0.00424%, 50/1179988 alleles, homozygotes = 0); grpmax FAF= 3.259e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 7.08275e-06; MAF= 0.00071%, 2/282376 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 1.55072e-05; MAF= 0.00155%, 2/128972 alleles, homozygotes = 0).
SpliceAI and Pangolin
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
BP4 SupportingBP4 is met under the MM-VCEP specification for synonymous variants. The VCEP rule for synonymous variants requires SpliceAI ≤0.20. SpliceAI predicts no significant splice impact (max delta score = 0.02), which is well below the 0.20 threshold. Multiple lines of computational evidence suggest no impact on splicing. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.02 ≤ 0.20 (BP4 threshold for synonymous variants)
Sources
BP7 SupportingBP7 is met under the MM-VCEP specification. The variant is a synonymous change (c.624C>T, p.Ala208=) located in exon 4, not within the last 3 nucleotides preceding the canonical donor splice site (c.722-724) or the first nucleotide following the canonical acceptor splice site (c.533). SpliceAI predicts no splice impact (max delta = 0.02 ≤ 0.20). Conservation data is no longer required per the VCEP v3.1.0 update. Details ▾Hide ▴
Evidence considered
- Synonymous variant not in critical splice region (not in last 3 nt of exon 4
- not first nt after acceptor)
- SpliceAI max delta = 0.02 ≤ 0.20
Sources
PP3 PP3 for synonymous variants under the MM-VCEP requires SpliceAI ≥0.38, including the creation of cryptic novel splice sites. SpliceAI predicts no significant splice impact for this variant (max delta score = 0.02), which is far below the 0.38 threshold. REVEL score is not available for this variant. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.02
- below PP3 threshold of 0.38
- REVEL score not available
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.02).
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 23619275 ↗ACMG position statement on prenatal/preconception expanded carrier screening.No paper-specific finding is recorded.
-
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.
-
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.
-
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 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 24121147 ↗Appropriateness of newborn screening for α1-antitrypsin deficiency.Teckman J et al. · 2014No paper-specific finding is recorded.
-
PMID 25394175 ↗A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment.Hampel H et al. · 2015No paper-specific finding is recorded.
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PMID 33661592 ↗PMID:33661592No 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].No 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.
-
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
53 / 1,613,324 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.020
Open source ↗
ClinVar
2 Likely 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 ↗
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/532686/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/21-36206807-G-A?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr21-34834510-G-A?dataset=gn…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_001001890.2%3Ac.6…
- OncoKB ↗www.oncokb.org/gene/RUNX1/A208=
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=RUNX1+c.624C%3ET
- 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= 3.28514e-05; MAF= 0.00329%, 53/1613324 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 4.23733e-05; MAF= 0.00424%, 50/1179988 alleles, homozygotes = 0); grpmax FAF= 3.259e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 7.08275e-06; MAF= 0.00071%, 2/282376 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 1.55072e-05; MAF= 0.00155%, 2/128972 alleles, homozygotes = 0).
ClinVar
This variant has been reported in ClinVar as Likely benign (2 clinical laboratories) and as Likely Benign by ClinGen Myeloid Malignancy Variant Curation Expert Panel (expert panel). (ClinVarID = 532686)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.02).
Functional
OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.
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.