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LYFE SCIENCES
Project: HERA
NM_000051.4:c.8052_8055del
p.Gln2684HisfsTer8  ·  ATM
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Classification rationale
1

The ATM c.8052_8055del (p.Gln2684HisfsTer8; p.Q2684Hfs*8) variant has not been observed in somatic cancers in COSMIC and is reported in ClinVar as pathogenic.

clinvar ↗
2

This variant is absent from gnomAD v2.1 and v4.1, which is below the ATM PM2_Supporting threshold of ≤0.001% in gnomAD v4 and does not meet the BS1 (>0.05%) or BA1 (>0.5%) population thresholds.

gnomad_v2 ↗ gnomad_v4 ↗ cspec ↗
3

This 4-bp deletion causes a frameshift in exon 55 with a premature stop codon, and under the ATM VCEP framework that supports PVS1 at very strong strength; because the predicted stop is upstream of p.Arg3047, it also meets the ATM-specific truncation-based PM5 rule.

cspec ↗
4

SpliceAI predicts no significant splice impact for this variant, with a maximum delta score of 0.01, and the ATM PP3/BP4 computational rules are not applied to this exonic frameshift variant class.

spliceai ↗ cspec ↗
Applied criteria
Met
Not met
Not assessed
N/A
Very strong
Strong
Moderate
Supporting
Pathogenic evidence
PVS
PVS1
PS
PS1
PS2
PS3
PS4
PM
PM1
PM2
PM3
PM4
PM5
PM6
PP
PP1
PP2
PP3
PP4
PP5
Benign evidence
BA
BA1
BS
BS1
BS2
BS3
BS4
BP
BP1
BP2
BP3
BP4
BP5
BP6
BP7
PVS1
—
—
Rationale
Select a criterion to inspect its explanation.
Evidence used
  • —
Gaps remaining
  • —
Rule
—
Publications
—
Research and evidence
ClinVar evidence
02
ClinVar
This variant has been reported in ClinVar as Pathogenic (3 clinical laboratories). (ClinVarID = 827424)
ClinVar ↗
Functional evidence
03
Functional
OncoKB: Likely Oncogenic
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Loss-of-function; curated oncogenicity label: Likely Oncogenic.
OncoKB ↗
In silico evidence
04
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01).
SpliceAI ↗
COSMIC evidence
05
COSMIC
This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).
COSMIC ↗
Cancer hotspots evidence
06
Cancer hotspots Not found
This variant does not lie in a statistically significant hotspot.
ResidueQ2684
Hotspots ↗