About MYC
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
MYC c.314G>A, p.(Gly105Asp)
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: 1
Benign evidence criteria: 1
Pathogenic criteria applied · 1
PM2Supporting
PM2 · supporting
NM_002467.6:c.314G>A is absent from all queried population databases (gnomAD v2.1, v4.1, and gnomAD-Canada v1.0). Under generic ACMG/AMP thresholds, an allele frequency below 0.1% supports PM2 at the supporting level.
Benign criteria applied · 1
BP4Supporting
BP4 · supporting
Multiple lines of computational evidence suggest no significant impact on the gene product. REVEL score 0.202 is below the 0.5 pathogenicity threshold. BayesDel score -0.0945 predicts a benign effect. SpliceAI max delta score 0.01 predicts no splicing alteration. Collectively, these in silico tools converge on a neutral or benign prediction.
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: PM2 supporting, BP4 supporting; combination = 1 supporting + 1 supporting benign, 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
Not recorded
gnomAD v4.1 allele counts were not recorded for this variant.
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI score
0.010 maximum delta
Recorded SpliceAI maximum delta score: 0.010. Refer to the recorded PP3/BP4 rationale for interpretation.
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
5 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV52367541, n = 5 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.
27 criteria with recorded statuses: 2 met · 21 not met · 0 not assessed · 4 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_002467.6:c.314G>A (p.Gly105Asp) is absent from all population databases including gnomAD v2.1, v4.1, and gnomAD-Canada v1.0, meeting PM2 at the supporting level.
Multiple in silico tools predict no significant impact: REVEL score 0.202 (below pathogenicity threshold), BayesDel score -0.0945 (predicts benign), and SpliceAI max delta 0.01 (no splicing impact), meeting BP4 at the supporting level.
The variant has been reported in somatic cancers (COSMIC COSV52367541, n=5) but without variant-specific functional characterization.
No variant-specific functional studies, de novo reports, case-control data, cosegregation data, or ClinVar classifications are available for this variant.
Under generic ACMG/AMP 2015 combination rules, PM2_Supporting and BP4_Supporting offset each other, yielding no net evidence toward pathogenicity or benignity. The variant is classified as a Variant of Uncertain Significance (VUS).
No criteria match.
Met · 2
PM2 SupportingNM_002467.6:c.314G>A is absent from all queried population databases (gnomAD v2.1, v4.1, and gnomAD-Canada v1.0). Under generic ACMG/AMP thresholds, an allele frequency below 0.1% supports PM2 at the supporting level. Details ▾Hide ▴
Evidence considered
- Absent from gnomAD v2.1 (exomes). Absent from gnomAD v4.1 (genomes + exomes). Absent from gnomAD-Canada v1.0 (HostSeq genomes).
Sources
BP4 SupportingMultiple lines of computational evidence suggest no significant impact on the gene product. REVEL score 0.202 is below the 0.5 pathogenicity threshold. BayesDel score -0.0945 predicts a benign effect. SpliceAI max delta score 0.01 predicts no splicing alteration. Collectively, these in silico tools converge on a neutral or benign prediction. Details ▾Hide ▴
Evidence considered
- REVEL 0.202 (below pathogenicity threshold). BayesDel -0.0945 (predicts benign). SpliceAI max delta 0.01 (no splice impact).
Sources
Not met · 21 · evaluated, threshold not reached
PS1 No pathogenic variant with the same amino acid change (p.Gly105Asp) has been previously established in MYC. The variant is absent from ClinVar and no published report of a G105D pathogenic classification was identified. Details ▾Hide ▴
Evidence considered
- Absent from ClinVar
- no known pathogenic variant at this amino acid position.
Sources
PS2 No de novo occurrence of NM_002467.6:c.314G>A has been reported in a patient with a phenotype consistent with a MYC-associated disorder. Parental testing data are absent from ClinVar and the literature. Details ▾Hide ▴
Evidence considered
- No de novo reports in ClinVar or published literature. Exploratory literature search found no de novo evidence.
Still missing
- MYC lacks an established germline disease phenotype
- making de novo ascertainment inherently limited.
Sources
PS3 No variant-specific functional studies have been published that directly test the effect of p.Gly105Asp on MYC transactivation, transformation, or protein interaction. Gene-level evidence confirms the MYC transactivation domain (residues 1-143) is functionally critical, but no assay includes this exact variant. Details ▾Hide ▴
Evidence considered
- OncoKB reports Unknown Oncogenic Effect with no variant-specific functional data. COSMIC records n=5 somatic occurrences (COSV52367541) without functional annotation. Exploratory search identified only gene-level TAD functional context.
Still missing
- No functional assay (reporter
- Myc target gene expression
- transformation
- or protein interaction) directly testing c.314G>A.
Sources
PS4 No case-control study comparing the frequency of NM_002467.6:c.314G>A in affected individuals versus controls has been published. The variant is absent from gnomAD but absence alone does not constitute PS4-level evidence. Details ▾Hide ▴
Evidence considered
- Absent from gnomAD v2.1
- v4.1
- and gnomAD-Canada v1.0. No cohort study has screened MYC for germline variants in a disease context.
Still missing
- No case-control study available
- MYC is not a recognized Mendelian disease gene with a clear phenotype for prevalence-based criteria.
Sources
PM1 p.Gly105Asp is located within the MYC N-terminal transactivation domain (TAD, residues 1-143), a critical functional region. However, codon 105 is not a recognized mutational hotspot, and no data on benign variation within this domain are available to satisfy the PM1 requirement of low benign variation in a critical functional domain. Details ▾Hide ▴
Evidence considered
- Variant lies within MYC TAD (aa 1-143)
- a domain essential for MYC-mediated transcription and transformation. Cancer Hotspots does not identify codon 105 as a statistically significant hotspot. No benign variation map of the TAD has been published.
Still missing
- No mutational hotspot at codon 105
- no benign variation data for the MYC TAD in germline context.
Sources
PM5 No pathogenic variant with a different amino acid change at codon 105 (Gly105) has been identified in MYC. The PM5 candidate search retrieved zero same-residue comparator variants from ClinVar. Details ▾Hide ▴
Evidence considered
- Zero same-residue comparator variants found. PM5 candidate search did not identify any expert-panel P/LP or majority P/LP calls at Gly105.
Sources
pm5_candidatesclinvar ↗
PM6 No assumed de novo occurrence has been reported for NM_002467.6:c.314G>A. PM6 requires observation of the variant in a patient where maternity and paternity have not been confirmed. Details ▾Hide ▴
Evidence considered
- No de novo reports in ClinVar or published literature.
Still missing
- MYC lacks an established germline disease phenotype
- limiting ascertainment of de novo events.
Sources
PP1 No cosegregation data are available for NM_002467.6:c.314G>A. No families with MYC germline variants and multi-generational phenotype data have been reported. Details ▾Hide ▴
Evidence considered
- No published pedigrees or segregation analyses involving this variant.
Still missing
- No defined MYC-related germline phenotype for cosegregation analysis.
PP2 PP2 requires a gene with a low rate of benign missense variation where missense variants are a common mechanism of disease. MYC is not a well-established Mendelian disease gene with characterized benign variation rates; no germline disease registry exists for MYC missense variants. Details ▾Hide ▴
Evidence considered
- MYC lacks a characterized germline disease spectrum and benign missense variation map.
Still missing
- No data on benign missense variation rate in MYC.
PP3 Multiple in silico tools do not support a deleterious effect for NM_002467.6:c.314G>A. REVEL score 0.202 is below the 0.5 threshold for pathogenicity. BayesDel score -0.0945 predicts a benign effect (below 0). SpliceAI max delta score 0.01 predicts no splicing alteration. These lines of evidence do not converge on a damaging prediction. Details ▾Hide ▴
Evidence considered
- REVEL 0.202 (below 0.5 pathogenicity threshold). BayesDel -0.0945 (below 0
- predicting benign). SpliceAI max delta 0.01 (no splicing impact). HCI prior not available.
Sources
PP4 No patient phenotype or family history information is available for NM_002467.6:c.314G>A. PP4 requires the patient's phenotype or family history to be highly specific for a disease with a single genetic etiology, which has not been established for MYC. Details ▾Hide ▴
Evidence considered
- No patient-specific phenotype data available. MYC lacks a well-defined germline disease phenotype.
Still missing
- No proband phenotype information.
PP5 No reputable source has classified NM_002467.6:c.314G>A as pathogenic. The variant is absent from ClinVar and has not been reported by any clinical diagnostic laboratory. Details ▾Hide ▴
BA1 Allele frequency >1% is required for BA1. NM_002467.6:c.314G>A is absent from all population databases (gnomAD v2.1, v4.1, gnomAD-Canada v1.0). Details ▾Hide ▴
Evidence considered
- Absent from all population databases.
Sources
BS1 Allele frequency >0.3% is required for BS1. NM_002467.6:c.314G>A is absent from all population databases (gnomAD v2.1, v4.1, gnomAD-Canada v1.0). Details ▾Hide ▴
Evidence considered
- Absent from all population databases.
Sources
BS2 BS2 requires observation in healthy adults (homozygous for recessive, hemizygous for X-linked, or heterozygous for a dominant disorder with full penetrance). NM_002467.6:c.314G>A is absent from all population databases, including healthy control cohorts. Details ▾Hide ▴
Evidence considered
- Absent from all population databases.
Sources
BS3 No well-established functional studies have demonstrated that NM_002467.6:c.314G>A has no deleterious effect on MYC protein function or splicing. No variant-specific functional data are available. Details ▾Hide ▴
Evidence considered
- No published functional assay directly testing p.Gly105Asp for neutral effect.
Still missing
- No functional studies exist for this variant.
BS4 No segregation data are available to demonstrate lack of cosegregation with disease for NM_002467.6:c.314G>A. BS4 requires observation of the variant in an affected family member who does not share the disease phenotype. Details ▾Hide ▴
Evidence considered
- No family studies or segregation analyses available.
Still missing
- No pedigrees involving this variant.
BP1 BP1 requires a missense variant in a gene where only truncating variants cause disease. MYC lacks an established germline disease mechanism exclusively mediated by truncating variants. Without a defined MYC germline disease spectrum, BP1 cannot be satisfied. Details ▾Hide ▴
Evidence considered
- MYC germline disease mechanism is not well-defined
- no data support truncation-only pathogenesis.
Still missing
- No established germline disease mechanism for MYC.
BP2 No observation of NM_002467.6:c.314G>A in trans with a known pathogenic MYC variant has been reported. Biallelic inactivation is not a recognized disease mechanism for MYC. Details ▾Hide ▴
Evidence considered
- No reports of this variant in trans with a pathogenic MYC variant.
BP5 BP5 requires observation of NM_002467.6:c.314G>A in a case with an alternate molecular basis for disease. No such observation has been reported. Details ▾Hide ▴
Evidence considered
- No report of this variant co-occurring with an alternate molecular diagnosis.
BP6 No reputable source has classified NM_002467.6:c.314G>A as benign. The variant is absent from ClinVar with zero submissions. Details ▾Hide ▴
Not applicable · 4· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANM_002467.6:c.314G>A is a missense variant (p.Gly105Asp) and does not fall into the ClinGen SVI PVS1 null-variant buckets of nonsense, frameshift, canonical ±1,2 splice consensus, initiation codon, or exon deletion (PMC6185798). Details ▾Hide ▴
Evidence considered
- Variant is missense
- variant_bucket='other'
- apply_generic_pvs1_framework=false per pvs1_variant_assessment.
Sources
BP3 N/ABP3 applies to in-frame deletions/insertions in repetitive regions. NM_002467.6:c.314G>A is a missense substitution. Details ▾Hide ▴
Evidence considered
- Variant is a substitution
- not an in-frame indel.
BP7 N/ABP7 applies to synonymous (silent) variants and intronic variants outside canonical splice sites. NM_002467.6:c.314G>A is a missense variant resulting in p.Gly105Asp. Details ▾Hide ▴
Evidence considered
- Variant is missense
- not synonymous. SpliceAI predicts no splicing alteration (max delta 0.01)
- but BP7 is restricted to synonymous/non-coding variants.
Sources
PS5 N/APS5 is not a criterion in the standard ACMG/AMP 2015 variant interpretation framework (Richards et al. 2015, PMID:25741868). No VCEP/CSPEC extension for MYC defines a PS5 criterion. Details ▾Hide ▴
Evidence considered
- Not part of the standard ACMG/AMP 2015 framework.
Sources
generic_acmg_combination_rules
Identifiers
- Gene
- MYC
- Transcript
- NM_002467.6
- Coding (HGVS c.)
- NM_002467.6:c.314G>A
- Protein (HGVS p.)
- NP_002458.2:p.(Gly105Asp)
- GRCh38
- chr8:127738531 G>A
- GRCh37
- chr8:128750777 G>A
- COSMIC
- COSV52367541
Gene diagram
Every interpreted variant in MYC, mapped onto the exon structure of NM_002467.6. Select a row to find it on the plot.
MYCNM_002467.6
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 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
Allele count data not recorded
gnomAD v2.1
Allele count data not recorded
gnomAD-Canada v1.0
Allele count data not recorded
Statements
gnomAD v4.1
Absent from gnomAD v4.1.
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.202
- BayesDel
- -0.095
How the predictions were used
BP4 SupportingMultiple lines of computational evidence suggest no significant impact on the gene product. REVEL score 0.202 is below the 0.5 pathogenicity threshold. BayesDel score -0.0945 predicts a benign effect. SpliceAI max delta score 0.01 predicts no splicing alteration. Collectively, these in silico tools converge on a neutral or benign prediction. Details ▾Hide ▴
Evidence considered
- REVEL 0.202 (below pathogenicity threshold). BayesDel -0.0945 (predicts benign). SpliceAI max delta 0.01 (no splice impact).
Sources
PP3 Multiple in silico tools do not support a deleterious effect for NM_002467.6:c.314G>A. REVEL score 0.202 is below the 0.5 threshold for pathogenicity. BayesDel score -0.0945 predicts a benign effect (below 0). SpliceAI max delta score 0.01 predicts no splicing alteration. These lines of evidence do not converge on a damaging prediction. Details ▾Hide ▴
Evidence considered
- REVEL 0.202 (below 0.5 pathogenicity threshold). BayesDel -0.0945 (below 0
- predicting benign). SpliceAI max delta 0.01 (no splicing impact). HCI prior not available.
Sources
BP7 N/ABP7 applies to synonymous (silent) variants and intronic variants outside canonical splice sites. NM_002467.6:c.314G>A is a missense variant resulting in p.Gly105Asp. Details ▾Hide ▴
Evidence considered
- Variant is missense
- not synonymous. SpliceAI predicts no splicing alteration (max delta 0.01)
- but BP7 is restricted to synonymous/non-coding variants.
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01). REVEL score = 0.202. BayesDel score = -0.0945134.
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
Captured gnomAD v4.1 source record
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.010
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_002467.6%3Ac.314G%3EA
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/8-128750777-G-A?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr8-127738531-G-A?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/8-127738531-G-A
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_002467.6%3Ac.314G…
- OncoKB ↗www.oncokb.org/gene/MYC/G105D
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=214712711
- 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
Absent from gnomAD v4.1.
gnomAD v2.1
Absent from gnomAD v2.1.
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 = 0.01). REVEL score = 0.202. BayesDel score = -0.0945134.
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; COSV52367541, n = 5 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.