About MYC
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
MYC c.154_156del, p.(Gln52del)
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 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: 3
Benign evidence criteria: 0
Pathogenic criteria applied · 3
PM1Supporting
PM1 · supporting
The variant deletes glutamine at position 52, which lies within MYC Box I (MB1, residues 44–63), a well-characterized transactivation domain critical for MYC-mediated transcription and transformation. The in-frame deletion removes a residue from this critical functional domain. The residue-level cancerhotspots.org analysis did not identify a statistically significant hotspot at this position.
PM2Moderate
PM2 · moderate
This variant is absent or at extremely low frequency in population databases. In gnomAD v2.1, the allele frequency is 0.0016% (4/249,036 alleles, no homozygotes). In gnomAD v4.1, the allele frequency is 0.00093% (15/1,612,048 alleles, no homozygotes). Both are well below the 0.1% threshold for PM2. The variant is absent from gnomAD-Canada v1.0.
PM4Moderate
PM4 · moderate
NM_002467.5:c.154_156del is an in-frame 3-nucleotide deletion resulting in the loss of a single amino acid (p.Gln52del) in a non-repeat region of MYC. This protein length change satisfies the PM4 criterion for in-frame deletions in non-repeat regions.
Benign criteria applied · 0
No benign criterion marked as applied in the recorded assessment.
Recorded classification: Uncertain significance
gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: PM1 supporting, PM2 moderate, PM4 moderate; combination = 2 moderate + 1 supporting, 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
15 / 1,612,048 alleles
gnomAD v4.1: 15 / 1,612,048 alleles. Recorded AF 9.30493e-06. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.60619e-05; MAF= 0.00161%, 4/249036 alleles, homozygotes = 0) and has highest observed frequency in the Remaining individuals population (AF= 0.000329164; MAF= 0.03292%, 2/6076 alleles, homozygotes = 0); grpmax FAF= 2.94e-06.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI score
0.000 maximum delta
Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.
No listed criterion applied
SpliceAI ↗
ClinVar submissions
Not recorded
A ClinVar laboratory submission summary was not recorded.
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. MYC, a transcription factor, is altered by chromosomal rearrangement, amplification and overexpression in a variety of cancer types.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
25 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV52368232, n = 25 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.
29 criteria with recorded statuses: 3 met · 11 not met · 9 not assessed · 6 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_002467.5:c.154_156del (p.Gln52del) is an in-frame deletion of a single amino acid in exon 2 of MYC, encoding the MYC proto-oncogene transcription factor.
This variant deletes glutamine at position 52, located within the well-characterized MYC Box I (MB1) transactivation domain (residues 44–63). PM1 (supporting) is applied.
The variant is extremely rare in population databases: gnomAD v2.1 allele frequency = 0.0016% (4/249,036 alleles) and gnomAD v4.1 allele frequency = 0.00093% (15/1,612,048 alleles), with no homozygotes observed. PM2 (moderate) is applied.
As an in-frame deletion in a non-repeat region resulting in a protein length change (loss of one amino acid), PM4 (moderate) is applied.
PVS1 is not met: this in-frame deletion does not qualify as a predicted null variant under the ClinGen SVI PVS1 decision framework (variant bucket: other). Nonsense-mediated decay is not expected.
PS3 is not met: no well-established functional studies were identified for this variant. Literature review yielded zero PMIDs with variant-specific data. OncoKB reports unknown oncogenic effect.
This variant has been observed 25 times in somatic cancers (COSMIC COSV52368232) but has not been reported in ClinVar. No germline disease associations, de novo events, cosegregation data, or patient phenotypes are available.
SpliceAI predicts no splicing impact (max delta score = 0.00). In silico pathogenicity tools (REVEL, BayesDel) are not applicable to deletion variants.
No criteria match.
Met · 3
PM1 SupportingThe variant deletes glutamine at position 52, which lies within MYC Box I (MB1, residues 44–63), a well-characterized transactivation domain critical for MYC-mediated transcription and transformation. The in-frame deletion removes a residue from this critical functional domain. The residue-level cancerhotspots.org analysis did not identify a statistically significant hotspot at this position. Details ▾Hide ▴
Evidence considered
- MYC Box I (MB1) spans residues 44–63 and is a well-characterized transactivation domain
- p.Gln52del removes a single residue from within MB1
- Cancerhotspots.org: residue not statistically significant
Sources
PM2 ModerateThis variant is absent or at extremely low frequency in population databases. In gnomAD v2.1, the allele frequency is 0.0016% (4/249,036 alleles, no homozygotes). In gnomAD v4.1, the allele frequency is 0.00093% (15/1,612,048 alleles, no homozygotes). Both are well below the 0.1% threshold for PM2. The variant is absent from gnomAD-Canada v1.0. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: AF = 0.0016% (4/249
- 036)
- 0 homozygotes
- grpmax FAF = 2.94e-06
- gnomAD v4.1: AF = 0.00093% (15/1
- 612
- 048)
- grpmax FAF = 3.59e-06
- gnomAD-Canada: absent
Sources
PM4 ModerateNM_002467.5:c.154_156del is an in-frame 3-nucleotide deletion resulting in the loss of a single amino acid (p.Gln52del) in a non-repeat region of MYC. This protein length change satisfies the PM4 criterion for in-frame deletions in non-repeat regions. Details ▾Hide ▴
Evidence considered
- In-frame deletion of 3 nucleotides (c.154_156del) causing loss of Gln52
- No evidence that position 52 lies within a repetitive region
Not met · 11 · evaluated, threshold not reached
PVS1 NM_002467.5:c.154_156del is an in-frame deletion of a single amino acid (p.Gln52del) and does not fall into the ClinGen SVI PVS1 null-variant buckets (nonsense, frameshift, or canonical ±1,2 splice consensus variants). NMD is not expected. PVS1 is not applicable for this variant class under the generic ACMG framework. Details ▾Hide ▴
Evidence considered
- Variant bucket classified as 'other' by pvs1_variant_assessment
- In-frame deletion does not trigger NMD
- Apply_generic_pvs1_framework is false per ClinGen SVI PVS1 decision tree (PMC6185798)
Sources
PS1 No previously established pathogenic variant causing the same amino acid change (p.Gln52del) was identified. This variant is absent from ClinVar, and no alternative nucleotide change resulting in the same protein consequence is known to be pathogenic. Details ▾Hide ▴
PS3 No well-established in vitro or in vivo functional studies supporting a damaging effect were identified for NM_002467.5:c.154_156del. OncoKB reports unknown oncogenic effect, and no variant-specific functional data were found in the literature. COSMIC observations (n=25) represent somatic occurrence counts, not experimental functional evidence. Details ▾Hide ▴
Evidence considered
- OncoKB: unknown oncogenic effect
- no variant-specific functional evidence curated
- Literature pass: 0 PMIDs retrieved across all evidence sources
- COSMIC: 25 somatic observations (occurrence only
- not functional data)
Still missing
- No functional data for this variant or a systematically characterized range
Sources
PP3 Multiple lines of computational evidence do not support a deleterious effect. REVEL and BayesDel scores are not available for this deletion variant. SpliceAI predicts no significant splice impact (max delta score = 0.00). No HCI prior score is available for MYC. In silico tools designed for missense variants are not informative for in-frame deletions. Details ▾Hide ▴
Evidence considered
- SpliceAI: max delta = 0.00
- no splicing impact predicted
- REVEL: not available (not an SNV)
- BayesDel: not available (not an SNV)
- HCI prior: gene not supported
Still missing
- No validated in silico tools for in-frame deletion impact prediction
Sources
PP5 No reputable source has reported this variant as pathogenic. The variant is absent from ClinVar, and OncoKB classifies it as having unknown oncogenic effect. Details ▾Hide ▴
BA1 The allele frequency in population databases is well below the 1% BA1 threshold. gnomAD v2.1 AF = 0.0016% and gnomAD v4.1 AF = 0.00093%. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: AF = 0.0016% (far below 1% threshold)
- gnomAD v4.1: AF = 0.00093% (far below 1% threshold)
Sources
BS1 The allele frequency is well below the 0.3% BS1 threshold for non-VCEP adjudication. gnomAD v2.1 AF = 0.0016% and gnomAD v4.1 AF = 0.00093%. No subpopulation exceeds 0.3%. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: AF = 0.0016%
- max subpopulation AF = 0.033% (Remaining individuals)
- gnomAD v4.1: AF = 0.00093%
- max subpopulation AF = 0.0047% (Finnish)
Sources
BS2 No homozygotes are observed in gnomAD v2.1 or v4.1. No evidence that this variant has been observed in a healthy adult individual in the homozygous state or in trans with a known pathogenic variant. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: 0 homozygotes
- gnomAD v4.1: 0 homozygotes
Sources
BP3 BP3 applies to in-frame deletions or insertions in repetitive regions without known function. The deletion occurs at position 52 within MYC Box I, a well-characterized functional transactivation domain, not in a repetitive region of unknown function. Details ▾Hide ▴
Evidence considered
- Position 52 lies within MYC Box I (MB1)
- a known functional domain
- No evidence this is a repetitive region without function
BP4 Multiple lines of computational evidence do not conclusively suggest no impact. SpliceAI predicts no splicing impact (max delta = 0.00), but this only addresses splicing. REVEL, BayesDel, and HCI prior are unavailable for this deletion variant. There is insufficient in silico evidence to rule out a deleterious effect on protein function. Details ▾Hide ▴
Evidence considered
- SpliceAI: max delta = 0.00 (no splice impact
- but does not assess protein function)
- REVEL/BayesDel/HCI: not available for deletion variants
Still missing
- No validated in silico tools for assessing in-frame deletion impact on protein function
Sources
Not assessed · 9 · no assessment recorded
PS2 No de novo occurrence data are available for this variant. No family studies or parental testing results were identified in the case materials or literature. Details ▾Hide ▴
Still missing
- No de novo testing or parental data available
PS4 No case-control or cohort prevalence data comparing affected versus unaffected individuals are available for this variant. Details ▾Hide ▴
Still missing
- No case-control or cohort data available
PM6 No de novo occurrence data (assumed or confirmed) are available for this variant. No parental testing or family studies were identified. Details ▾Hide ▴
Still missing
- No de novo data or parental testing available
PP1 No cosegregation data are available for this variant. No family studies were identified in the case materials or literature. Details ▾Hide ▴
Still missing
- No family or cosegregation data available
PP4 No patient phenotype or clinical data are available for this case. PP4 requires that the patient's phenotype or family history is highly specific for a disease with a single genetic etiology. Details ▾Hide ▴
Still missing
- No patient phenotype or clinical data provided
BS3 No well-established in vitro or in vivo functional studies showing no deleterious effect were identified for this variant. No functional data of any kind were found in the literature. Details ▾Hide ▴
Still missing
- No functional data available to assess benign effect
BS4 No cosegregation or family data are available to evaluate lack of segregation with disease. Details ▾Hide ▴
Still missing
- No family or segregation data available
BP2 No evidence that this variant has been observed in trans with a known pathogenic variant in a gene associated with a fully penetrant dominant disorder. Details ▾Hide ▴
Still missing
- No trans phase data available
BP5 No data are available regarding an alternate molecular basis for disease in a case harboring this variant. Details ▾Hide ▴
Still missing
- No alternate molecular basis data available
Not applicable · 6· recorded as not applicable Show reasons ▾Hide reasons ▴
PM3 N/APM3 applies to recessive disorders where the variant is detected in trans with a pathogenic variant. MYC is not associated with a recessive germline disorder; this criterion is not applicable. Details ▾Hide ▴
No further detail was recorded.
PM5 N/APM5 applies to novel missense changes at an amino acid residue where a different missense change has been determined to be pathogenic. NM_002467.5:c.154_156del is an in-frame deletion, not a missense variant. PM5 candidate harvesting was attempted but could not confirm classic same-residue PM5 semantics for this variant class. Details ▾Hide ▴
Evidence considered
- Variant is an in-frame deletion
- not a missense change
- pm5_candidates.json: no eligible same-residue comparators identified
PP2 N/APP2 applies to missense variants in genes where missense variation is an established mechanism and benign missense variation is rare. NM_002467.5:c.154_156del is an in-frame deletion, not a missense variant. Details ▾Hide ▴
No further detail was recorded.
BP1 N/ABP1 applies to missense variants in genes where a truncating mechanism is the primary cause of disease. NM_002467.5:c.154_156del is an in-frame deletion, not a missense variant. Details ▾Hide ▴
No further detail was recorded.
BP7 N/ABP7 applies to synonymous variants for which splicing prediction algorithms predict no impact on the splice consensus sequence nor the splice enhancer. NM_002467.5:c.154_156del is an in-frame deletion, not a synonymous variant. Details ▾Hide ▴
No further detail was recorded.
PS5 N/APS5 is not a standard ACMG/AMP 2015 criterion. No criterion definition available under generic ACMG framework. Details ▾Hide ▴
No further detail was recorded.
Identifiers
- Gene
- MYC
- Transcript
- NM_002467.5
- Coding (HGVS c.)
- NM_002467.5:c.154_156del
- Protein (HGVS p.)
- NP_002458.2:p.(Gln52del)
- GRCh38
- chr8:127738358 CCAG>C
- GRCh37
- chr8:128750604 CCAG>C
- COSMIC
- COSV52368232
Gene diagram
Every interpreted variant in MYC, mapped onto the exon structure of NM_002467.5. Select a row to find it on the plot.
MYCNM_002467.5
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 MYC
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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
15 / 1,612,048 alleles
AF 9.3e-06 · 0 homozygotes · FAF 3.59e-06
gnomAD v2.1
4 / 249,036 alleles
AF 1.61e-05 · 0 homozygotes · FAF 2.94e-06
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 9.3e-06 · 15 / 1,612,048 alleles · 0 hom · FAF 3.6e-06
| European (Finnish)3 / 63,906 | 4.7e-05 |
| East Asian1 / 44,828 | 2.2e-05 |
| Remaining individuals1 / 62,402 | 1.6e-05 |
| African/African American1 / 75,000 | 1.3e-05 |
| European (non-Finnish)9 / 1,178,650 | 7.6e-06 |
0 alternate alleles recorded in 5 other groups: Admixed American, Amish, Middle Eastern, South Asian, Ashkenazi Jewish.
gnomAD v2.1
AF 1.6e-05 · 4 / 249,036 alleles · 0 hom · FAF 2.9e-06
| Remaining individuals2 / 6,076 | 0.00033 |
| European (non-Finnish)2 / 112,860 | 1.8e-05 |
0 alternate alleles recorded in 6 other groups: African/African American, Admixed American, Ashkenazi Jewish, East Asian, European (Finnish), South Asian.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 9.30493e-06; MAF= 0.00093%, 15/1612048 alleles, homozygotes = 0) and has highest observed frequency in the European (Finnish) population (AF= 4.69439e-05; MAF= 0.00469%, 3/63906 alleles, homozygotes = 0); grpmax FAF= 3.59e-06.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.60619e-05; MAF= 0.00161%, 4/249036 alleles, homozygotes = 0) and has highest observed frequency in the Remaining individuals population (AF= 0.000329164; MAF= 0.03292%, 2/6076 alleles, homozygotes = 0); grpmax FAF= 2.94e-06.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
PP3 Multiple lines of computational evidence do not support a deleterious effect. REVEL and BayesDel scores are not available for this deletion variant. SpliceAI predicts no significant splice impact (max delta score = 0.00). No HCI prior score is available for MYC. In silico tools designed for missense variants are not informative for in-frame deletions. Details ▾Hide ▴
Evidence considered
- SpliceAI: max delta = 0.00
- no splicing impact predicted
- REVEL: not available (not an SNV)
- BayesDel: not available (not an SNV)
- HCI prior: gene not supported
Still missing
- No validated in silico tools for in-frame deletion impact prediction
Sources
BP4 Multiple lines of computational evidence do not conclusively suggest no impact. SpliceAI predicts no splicing impact (max delta = 0.00), but this only addresses splicing. REVEL, BayesDel, and HCI prior are unavailable for this deletion variant. There is insufficient in silico evidence to rule out a deleterious effect on protein function. Details ▾Hide ▴
Evidence considered
- SpliceAI: max delta = 0.00 (no splice impact
- but does not assess protein function)
- REVEL/BayesDel/HCI: not available for deletion variants
Still missing
- No validated in silico tools for assessing in-frame deletion impact on protein function
Sources
BP7 N/ABP7 applies to synonymous variants for which splicing prediction algorithms predict no impact on the splice consensus sequence nor the splice enhancer. NM_002467.5:c.154_156del is an in-frame deletion, not a synonymous variant. Details ▾Hide ▴
No further detail was recorded.
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
0 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata.
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
15 / 1,612,048 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
Captured ClinVar source record
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/?term=NM_002467.5%3Ac.154_156del
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/8-128750604-CCAG-C?dataset=gn…
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr8-127738358-CCAG-C?dataset…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/8-127738358-CCAG-C
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_002467.5%3Ac.154_…
- OncoKB ↗www.oncokb.org/gene/MYC/Q52del
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=214698041
- 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= 9.30493e-06; MAF= 0.00093%, 15/1612048 alleles, homozygotes = 0) and has highest observed frequency in the European (Finnish) population (AF= 4.69439e-05; MAF= 0.00469%, 3/63906 alleles, homozygotes = 0); grpmax FAF= 3.59e-06.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.60619e-05; MAF= 0.00161%, 4/249036 alleles, homozygotes = 0) and has highest observed frequency in the Remaining individuals population (AF= 0.000329164; MAF= 0.03292%, 2/6076 alleles, homozygotes = 0); grpmax FAF= 2.94e-06.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
ClinVar
This variant is absent from ClinVar.
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
Functional
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. MYC, a transcription factor, is altered by chromosomal rearrangement, amplification and overexpression in a variety of cancer types.
Somatic
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV52368232, n = 25 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.