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LYFE SCIENCES
Project: HERA
NM_001369787.1:c.531_533del
p.Lys180del  ·  KRAS
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Classification rationale
1

The KRAS c.531_533del (p.Lys180del) variant has not been observed in COSMIC and is reported in ClinVar as Benign with expert panel review.

clinvar ↗
2

This variant is present in gnomAD v2.1 at 0.05904% overall and 0.10364% in the highest-frequency subpopulation, and in gnomAD v4.1 at 0.10753% overall and 0.13901% in the highest-frequency subpopulation, exceeding the KRAS RASopathy VCEP BA1 threshold of 0.05% and BS1 threshold of 0.025%.

gnomad_v2 ↗ gnomad_v4 ↗ cspec ↗
3

Computational evidence does not support a disease-relevant splicing effect; SpliceAI showed a maximum delta score of 0.29, and no REVEL or BayesDel score was available for this in-frame deletion.

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
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Rationale
Select a criterion to inspect its explanation.
Evidence used
  • —
Gaps remaining
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Rule
—
Publications
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Research and evidence
gnomAD v2.1 evidence
v2.1
gnomAD v4.1 evidence
v4.1
01
Population
gnomAD v2.1This variant is present in gnomAD v2.1 (AF= 0.000590445; MAF= 0.05904%, 166/281144 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 0.00103636; MAF= 0.10364%, 133/128334 alleles, homozygotes = 0); grpmax FAF= 0.00089964.
gnomAD v4.1This variant is present in gnomAD v4.1 (AF= 0.00107527; MAF= 0.10753%, 1732/1610758 alleles, homozygotes = 2) and has highest observed frequency in the European (non-Finnish) population (AF= 0.00139014; MAF= 0.13901%, 1637/1177578 alleles, homozygotes = 2); grpmax FAF= 0.00133394.
gnomAD v2 ↗ gnomAD v4 ↗
ClinVar evidence
02
ClinVar
This variant has been reported in ClinVar as Likely benign (10 clinical laboratories) and as Benign (2 clinical laboratories) and as Likely Benign (1 clinical laboratory) and as Benign by ClinGen RASopathy Variant Curation Expert Panel (expert panel). (ClinVarID = 45129)
ClinVar ↗
Functional evidence
03
Functional
OncoKB: 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. KRAS, a GTPase which functions as an upstream regulator of the MAPK pathway, is frequently mutated in various cancer types including lung, colorectal
OncoKB ↗
In silico evidence
04
In silico
SpliceAI predicts possible splice impact for this variant (max delta score = 0.29).
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.
ResidueK180
Hotspots ↗