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LYFE SCIENCES
Project: HERA
NM_000059.4:c.4071A>C
p.Leu1357=  ·  BRCA2
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Legacy Engine
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Classification rationale
1

BRCA2 ENIGMA BA1 is met because the variant exceeds the stand-alone benign frequency threshold in gnomAD: v2.1 grpmax FAF 0.00161392 and v4.1 grpmax FAF 0.00154091, both >0.001.

gnomad_v2 ↗
2

The variant is synonymous, p.(Leu1357=), and lies outside the BRCA2 clinically important domains defined by ENIGMA; with SpliceAI max delta score 0.00, this satisfies BP1_Strong.

cspec ↗
3

ClinVar shows a concordant benign expert-panel assertion from ENIGMA, which supports but does not replace the VCEP rule-based classification.

clinvar ↗
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
  • —
Rule
—
Publications
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Research and evidence
ClinVar evidence
02
ClinVar
This variant has been reported in ClinVar as Benign (8 clinical laboratories) and as Likely benign (4 clinical laboratories) and as Benign by Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) (expert panel).
ClinVar ↗
Functional evidence
03
Functional
OncoKB oncogenicity for this specific variant: Unknown Oncogenic Effect (variant has not been individually curated).
OncoKB ↗
In silico evidence
04
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
SpliceAI ↗
COSMIC evidence
05
COSMIC
This variant has not previously been reported in somatic cancers (COSMIC).
Cancer hotspots evidence
06
Cancer hotspots
No cancer hotspot summary recorded.