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Variant interpretation report

BRCA2 c.1909+11_1909+12del, p.?

NM_000059.4:c.1909+11_1909+12del NP_000050.3:p.? View identifiers
Classification
Likely benign

Variant description:

No variant summary was recorded for this case.

Five-step scale from benign to pathogenic. This variant is likely benign. Select a step to read what it means.

Likely benign.A likely benign classification under the recorded framework.

In plain language

Gene-level background from the recorded interpretation.

About BRCA2

No gene-level summary was recorded for this case.

LYFE Sciences is an AI system, and it can make mistakes. Criteria may be applied incorrectly, sources may be misread, and a confident-looking classification can still be wrong. Double-check every criterion and its underlying evidence before relying on any call.
01The reasoning

How it was classified

The recorded framework is ClinGen BRCA2 VCEP v1.2.0. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.

Recorded applied criteria

The applied criteria and their strengths are shown as assessed under the stated framework.

Pathogenic evidence criteria: 0 Benign evidence criteria: 2
Pathogenic criteria applied · 0

No pathogenic criterion marked as applied in the recorded assessment.

Benign criteria applied · 2
BP4Supporting
BP4 · supporting

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, ≤0.1). BP4_Supporting is met per ENIGMA BRCA2 specification Figure 1A.

BP7Supporting
BP7 · supporting

The intronic deletion is located at position +11, outside the conserved donor motif (beyond +7). BP4 is met (SpliceAI max delta = 0.00 ≤ 0.1). BP7_Supporting is met per ENIGMA BRCA2 specification Figure 1A and Appendix J.

Recorded classification: Likely benign

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.

02The sources

Evidence at a glance

Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.

SpliceAI score
0.000 maximum delta

Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.

ClinVar submissions
Not recorded

A ClinVar laboratory submission summary was not recorded.

Context only ClinVar ↗
No screenshot for this evidence
Functional evidence
Not recorded

No standalone functional evidence summary is recorded in evidence_summary.functional.

No listed criterion applied OncoKB ↗
Somatic evidence
No matching record reported

This variant has not previously been reported in somatic cancers (COSMIC).

Context only COSMIC ↗
For specialists

Technical detail

ACMG/AMP criteria under ClinGen BRCA2 VCEP v1.2.0, with the data and sources behind each one.

28 criteria with recorded statuses: 2 met · 5 not met · 8 not assessed · 13 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Met Not met Not assessed Not applicable

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.

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.

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.

Met · 2

BP4 SupportingNM_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, ≤0.1). BP4_Supporting is met per ENIGMA BRCA2 specification Figure 1A. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta = 0.00 ≤ 0.1
  • Intronic deletion at +11/+12
  • outside canonical +/-1
  • 2 donor splice sites
Sources
BP7 SupportingThe intronic deletion is located at position +11, outside the conserved donor motif (beyond +7). BP4 is met (SpliceAI max delta = 0.00 ≤ 0.1). BP7_Supporting is met per ENIGMA BRCA2 specification Figure 1A and Appendix J. Details ▾Hide ▴
Evidence considered
  • Intronic variant at +11 position
  • outside conserved donor motif (beyond +7)
  • BP4 met (SpliceAI max delta = 0.00 ≤ 0.1)
Sources

Not met · 5 · evaluated, threshold not reached

PVS1 NM_000059.4:c.1909+11_1909+12del is an intronic deletion at positions +11 and +12 of intron 10, outside the canonical donor splice consensus (+/-1,2). Does not meet ENIGMA PVS1 null-variant criteria (nonsense, frameshift, canonical +/-1,2 splice, initiation codon, or exon-level deletion). Details ▾Hide ▴
Evidence considered
  • Intronic deletion at +11/+12
  • outside canonical +/-1
  • 2 splice consensus
Sources
PS1 SpliceAI predicts no splicing impact (max delta = 0.00). No previously classified pathogenic variant with the same predicted splicing effect available as comparator. PS1 is not met. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta = 0.00
  • no splicing impact predicted
Sources
PP3 SpliceAI predicts no significant splice impact (max delta = 0.00), well below the ENIGMA PP3 threshold of SpliceAI ≥0.2 for intronic variants outside donor/acceptor +/-1,2 sites. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta = 0.00
  • below ENIGMA PP3 threshold of ≥0.2
Sources
BA1 Variant is absent from gnomAD v2.1 and v4.1. BA1 threshold (FAF > 0.1% in non-founder populations) is not met. Details ▾Hide ▴
Evidence considered
  • Absent from gnomAD v2.1 and v4.1
Sources
BS1 Variant is absent from gnomAD v2.1 and v4.1. Does not meet ENIGMA BS1 thresholds (FAF > 0.00002 for Supporting; FAF > 0.0001 for Strong). Details ▾Hide ▴
Evidence considered
  • Absent from gnomAD v2.1 and v4.1
Sources

Not assessed · 8 · no assessment recorded

PS3 No functional assay data available for this intronic deletion variant in ENIGMA Specifications Table 9 or published literature. Details ▾Hide ▴
Still missing
  • No functional assay data for this intronic deletion
PS4 Variant is absent from ClinVar and COSMIC. No case-control study data available for prevalence comparison per ENIGMA PS4 specification. Details ▾Hide ▴
Evidence considered
  • Absent from ClinVar
  • no case-control data
Still missing
  • No case-control study data available
Sources
PP1 No co-segregation data available for quantitative analysis per ENIGMA PP1 specification. Details ▾Hide ▴
Still missing
  • No co-segregation data available
PP4 Variant is not listed in the Li et al. 2020 (PMID:31853058) BRCA2 clinical-history likelihood-ratio table. No clinical-history LR data available for PP4 assessment. Details ▾Hide ▴
Evidence considered
  • Variant absent from Li et al. 2020 BRCA2 clinical_history_LR table
Still missing
  • No clinical-history LR data for this variant
Sources
BS2 No proband-level data available to evaluate for BS2 points under ENIGMA Specifications Table 8 (absence of Fanconi Anemia phenotype). Details ▾Hide ▴
Still missing
  • No proband phenotype data available
BS3 No functional assay data available for this intronic deletion variant in ENIGMA Specifications Table 9 or published literature. Details ▾Hide ▴
Still missing
  • No functional assay data for this intronic deletion
BS4 No segregation data available for quantitative BS4 likelihood-ratio analysis per ENIGMA specification. Details ▾Hide ▴
Still missing
  • No segregation data available
BP5 Variant is not listed in the Li et al. 2020 (PMID:31853058) BRCA2 clinical-history likelihood-ratio table. No clinical-history LR data available for BP5 assessment. Details ▾Hide ▴
Evidence considered
  • Variant absent from Li et al. 2020 BRCA2 clinical_history_LR table
Still missing
  • No clinical-history LR data for this variant
Sources
Not applicable · 13· recorded as not applicable Show reasons ▾Hide reasons ▴
PS2 VCEPPS2 is not applicable for this VCEP per ClinGen ENIGMA BRCA1/2 specification v1.2. Details ▾Hide ▴
Sources
PM1 VCEPPM1 is not applicable for this VCEP; captured by bioinformatic analysis (PP3/BP4) per ENIGMA BRCA2 specification. Details ▾Hide ▴
Sources
PM2 N/APM2 is not applicable for deletion variants per ENIGMA BRCA2 specification v1.2: 'Do not apply for insertion, deletion or delins variants.' Details ▾Hide ▴
Evidence considered
  • Variant is a deletion
  • PM2 explicitly excluded by ENIGMA specification
Sources
PM4 VCEPPM4 is not applicable for this VCEP per ENIGMA BRCA1/2 specification v1.2. Details ▾Hide ▴
Sources
PM5 N/APM5 in ENIGMA BRCA2 is repurposed for PTC comparator logic (PM5_PTC). This intronic deletion at +11/+12 is not a protein termination codon variant and is not located in an exon. Details ▾Hide ▴
Evidence considered
  • Intronic variant
  • not a PTC
  • not in an exon with established pathogenic PTC comparators
Sources
PM6 VCEPPM6 is not applicable for this VCEP per ENIGMA BRCA1/2 specification v1.2. Details ▾Hide ▴
Sources
PP2 VCEPPP2 is not applicable for this VCEP per ENIGMA BRCA1/2 specification v1.2. Details ▾Hide ▴
Sources
PP5 VCEPPP5 is not applicable for this VCEP per ClinGen Sequence Variant Interpretation VCEP Review Committee recommendation. Details ▾Hide ▴
Sources
BP1 N/ABP1 applies to coding-region variants (silent, missense, in-frame indels). This is an intronic deletion at +11/+12, outside the coding region. Details ▾Hide ▴
Evidence considered
  • Intronic variant
  • not a coding-region variant type for BP1
Sources
BP2 VCEPBP2 is not applicable for this VCEP per ENIGMA BRCA1/2 specification v1.2. Details ▾Hide ▴
Sources
BP3 VCEPBP3 is not applicable for this VCEP; captured by bioinformatic tool prediction and domain analysis per ENIGMA specification. Details ▾Hide ▴
Sources
BP6 VCEPBP6 is not applicable for this VCEP per ENIGMA BRCA1/2 specification v1.2. Details ▾Hide ▴
Sources
PS5 N/APS5 is not applicable for this VCEP per ClinGen recommendations. Details ▾Hide ▴
Sources

Identifiers

Gene
BRCA2
Transcript
NM_000059.4
Coding (HGVS c.)
NM_000059.4:c.1909+11_1909+12del
Protein (HGVS p.)
NP_000050.3:p.?
GRCh38
chr13:32333396 GTC>G
GRCh37
chr13:32907533 GTC>G

Gene diagram

Every interpreted variant in BRCA2, mapped onto the exon structure of NM_000059.4. Select a row to find it on the plot.

BRCA2NM_000059.4
Fetching transcript structure from UCSC…
gnomAD v4.1 Allele count data not recorded
gnomAD v2.1 Allele count data not recorded
gnomAD-Canada v1.0 0 / 0 alleles AF 0 · 0 homozygotes · FAF 0

By genetic ancestry

gnomAD-Canada

AF 0 · 0 / 0 alleles · 0 hom

Statements

gnomAD v4.1

Absent from gnomAD v4.1.

gnomAD v2.1

Absent from gnomAD v2.1.

Open the gnomAD-Canada detail page →

SpliceAI and Pangolin

Pangolin splice lossmagnitude shown
-0.050
Pangolin splice gain
0.040

Other predictors

REVEL
Not available
BayesDel
Not available

How the predictions were used

BP4 SupportingNM_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, ≤0.1). BP4_Supporting is met per ENIGMA BRCA2 specification Figure 1A. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta = 0.00 ≤ 0.1
  • Intronic deletion at +11/+12
  • outside canonical +/-1
  • 2 donor splice sites
Sources
BP7 SupportingThe intronic deletion is located at position +11, outside the conserved donor motif (beyond +7). BP4 is met (SpliceAI max delta = 0.00 ≤ 0.1). BP7_Supporting is met per ENIGMA BRCA2 specification Figure 1A and Appendix J. Details ▾Hide ▴
Evidence considered
  • Intronic variant at +11 position
  • outside conserved donor motif (beyond +7)
  • BP4 met (SpliceAI max delta = 0.00 ≤ 0.1)
Sources
PP3 SpliceAI predicts no significant splice impact (max delta = 0.00), well below the ENIGMA PP3 threshold of SpliceAI ≥0.2 for intronic variants outside donor/acceptor +/-1,2 sites. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta = 0.00
  • below ENIGMA PP3 threshold of ≥0.2
Sources

Statement

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).

0 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata.

Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.

All source links

Statements for reports

The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.

gnomAD v4.1

Absent from gnomAD v4.1.

gnomAD v2.1

Absent from gnomAD v2.1.

ClinVar

This variant is absent from ClinVar.

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).

Somatic

This variant has not previously been reported in somatic cancers (COSMIC).