Back
LYFE SCIENCES
Project: HERA
NM_007294.4:c.5089T>C
p.Cys1697Arg  ·  BRCA1
Starting
Initialising…
0%
Legacy Engine
Processing…
Classification rationale
1

The BRCA1 c.5089T>C (p.Cys1697Arg) variant has been reported in ClinVar as Pathogenic by the ClinGen ENIGMA expert panel and is listed in OncoKB as Likely Oncogenic with loss-of-function effect.

clinvar ↗ oncokb ↗
2

This variant is absent from gnomAD v2.1 and gnomAD v4.1, supporting rarity in population databases.

gnomad_v2 ↗ gnomad_v4 ↗
3

Calibrated BRCA1 functional studies compiled by ENIGMA show complete functional impact/loss of function for p.(Cys1697Arg), supporting PS3_Strong.

4

The variant lies within the BRCA1 BRCT repeat region, has a BayesDel score of 0.398 which is above the PP3 threshold of 0.28, and SpliceAI predicts no significant splice effect with a maximum delta score of 0.08, supporting PP3.

cspec ↗ spliceai ↗
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 Likely pathogenic (6 clinical laboratories) and as Pathogenic (5 clinical laboratories) and as Uncertain significance (2 clinical laboratories) and as Pathogenic by ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel, ClinGen (expert panel).
ClinVar ↗
Functional evidence
03
Functional
OncoKB: Likely Oncogenic
OncoKB classifies this variant as Likely Oncogenic; biological effect: Loss-of-function.
OncoKB ↗
In silico evidence
04
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.08).
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.
ResidueC1697
Hotspots ↗