Starting
Initialising…
0%
MYC
Final classification
VUS
MYC c.314G>A · p.Gly105Asp
MYC

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.

Gene
MYC
Transcript
NM_002467.6
HGVS · transcript:coding
NM_002467.6:c.314G>A
Consequence
N/A
GRCh38
chr8:127738531 G>A
GRCh37
chr8:128750777 G>A
Basis 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.
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.
Classification rationale
PM2 BP4 VUS
MYC c.314G>A

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.1 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.2 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.3 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).4

PM2 + BP4 VUS
2 revelbayesdelspliceai ↗
4 generic_acmg_combination_rules
Gene diagram · NM_002467.6 · variants mapped to exon structure
MYC NM_002467.6
Fetching transcript structure from UCSC…
Applied criteria · 2 met · select any tile
Met
Not met
Not assessed
N/A
Strength very strong supporting
Pathogenic evidence
PVS
PS
PM
PP
Benign evidence
BA
BS
BP
Rationale
Select a criterion.
Sources
Evidence used
    Gaps remaining
      Rule
      Research & evidence
      Population frequency
      gnomAD v4.1 screenshot
      gnomAD v4.1
      gnomAD v2.1 screenshot
      gnomAD v2.1
      v4.1
      Absent from gnomAD v4.1.
      v2.1
      Absent from gnomAD v2.1.
      🇨🇦 CA
      Absent from gnomAD-Canada v1.0.
      Allele frequency by ancestry
      three datasets · side by side
      gnomAD v4.1
      Absent · 0 / ?
      0 hom
      Not observed in any ancestry group.
      gnomAD v2.1
      Absent · 0 / ?
      0 hom
      Not observed in any ancestry group.
      gnomAD Canada 🇨🇦
      Absent · 0 / ?
      0 hom
      Not observed in any ancestry group.
      ClinVar screenshot
      ClinVar
      This variant is absent from ClinVar.
      SpliceAI screenshot
      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 screenshot
      Functional Unknown Oncogenic Effect
      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.
      OncoKB ↗
      COSMIC screenshot
      COSMIC
      Cancer hotspots screenshot
      Cancer hotspots
      Somatic evidence Not in COSMIC / hotspots
      COSMIC
      This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV52367541, n = 5 times).
      Hotspots
      This variant does not lie in a statistically significant hotspot.
      Sources & reference links
      8Sources
      ClinVar
      gnomAD v2.1
      gnomAD v4.1
      gnomAD-Canada
      SpliceAI
      OncoKB
      COSMIC
      Cancer hotspots