Starting
Initialising…
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BRCA2
Final classification
Likely Benign
BRCA2 c.1909+11_1909+12del · p.?
BRCA2

NM_000059.4:c.1909+11_1909+12del is an intronic deletion at positions +11 and +12 of intron 10, outside the native donor splice consensus (+/-1,2). SpliceAI predicts no splicing impact (max delta = 0.00). BP4_Supporting is met per ENIGMA BRCA2 specification Figure 1A.

Gene
BRCA2
Transcript
NM_000059.4
HGVS · transcript:coding
NM_000059.4:c.1909+11_1909+12del
Consequence
N/A
GRCh38
chr13:32333396 GTC>G
GRCh37
chr13:32907533 GTC>G
Basis ENIGMA BRCA1/BRCA2 Specification v1.2 Table 3: two Supporting (Benign) criteria (BP4_Supporting, BP7_Supporting) met, zero pathogenic criteria met. Matches the likely_benign rule requiring >=2 Supporting (Benign) criteria.
ENIGMA BRCA1/BRCA2 Specification v1.2 Table 3: two Supporting (Benign) criteria (BP4_Supporting, BP7_Supporting) met, zero pathogenic criteria met. Matches the likely_benign rule requiring >=2 Supporting (Benign) criteria.
Classification rationale
BP4BP7 Likely Benign
BRCA2 c.1909+11_1909+12del

NM_000059.4:c.1909+11_1909+12del is an intronic deletion at positions +11 and +12 of intron 10, outside the native donor splice consensus (+/-1,2). SpliceAI predicts no splicing impact (max delta = 0.00). BP4_Supporting is met per ENIGMA BRCA2 specification Figure 1A.1 The variant is located at intronic position +11, outside the conserved donor motif (beyond +7). BP4 is met (SpliceAI ≤0.1). BP7_Supporting is met per ENIGMA BRCA2 specification Figure 1A and Appendix J.2 No pathogenic criteria are met. PVS1 is not met (outside canonical +/-1,2 splice consensus; does not qualify as a null variant per ENIGMA PVS1 criteria). PM2 is explicitly not applicable for deletion variants per ENIGMA specification. PP3 is not met (SpliceAI max delta = 0.00 < 0.2). Two supporting benign criteria are met (BP4_Supporting, BP7_Supporting). Per ENIGMA Table 3 combining rules, ≥2 Supporting (Benign) criteria supports classification as Likely Benign.3

BP4 + BP7 Likely Benign
Gene diagram · NM_000059.4 · variants mapped to exon structure
BRCA2 NM_000059.4
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 · supports benign
      gnomAD v4.1 screenshot
      gnomAD v4.1
      gnomAD v2.1 screenshot
      gnomAD v2.1
      Population frequency
      Absent from gnomAD v4.1.
      Absent from gnomAD v2.1.
      This variant is absent from gnomAD-Canada.
      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 = 0.00).
      Functional No data
      No calibrated functional assay or RNA evidence was identified for this variant.
      OncoKB ↗
      COSMIC screenshot
      COSMIC
      Somatic evidence
      COSMIC
      This variant has not previously been reported in somatic cancers (COSMIC).
      Hotspots
      This variant does not lie in a statistically significant cancer hotspot.
      COSMIC ↗
      Sources & reference links
      7Sources
      CSpec VCEP
      ClinVar
      gnomAD v2.1
      gnomAD v4.1
      SpliceAI
      OncoKB
      COSMIC