0%
BRCA2c.7759C>TLikely benign
Print report
Variant interpretation report

BRCA2 c.7759C>T, p.(Leu2587Phe)

NM_000059.3:c.7759C>T NP_000050.2:p.(Leu2587Phe) 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: 4
Pathogenic criteria applied · 0

No pathogenic criterion marked as applied in the recorded assessment.

Benign criteria applied · 4
BS1Supporting
BS1 · supporting

This variant meets BS1 at Supporting strength because its filter allele frequency exceeds the ENIGMA BRCA2 BS1 Supporting threshold of 0.00002 but does not exceed the Strong threshold of 0.0001. In gnomAD v2.1, grpmax FAF is 4.115e-05, and in gnomAD v4.1, grpmax FAF is 4.535e-05.

BS3Strong
BS3 · strong

This variant meets BS3 at Strong strength. In the ENIGMA BRCA2 curated functional assay table, two calibrated studies reported protein function similar to benign control variants, supporting a benign functional interpretation.

BP4Supporting
BP4 · supporting

This variant meets BP4 at Supporting strength under the ENIGMA BRCA2 computational rule. Codon 2587 is within the BRCA2 DNA-binding domain, BayesDel no-AF is 0.147986, which is at or below the BP4 threshold of 0.18, and SpliceAI shows a maximum delta score of 0.04, which is at or below the BP4 threshold of 0.1. REVEL is 0.73, but the official ENIGMA BRCA2 rule for this criterion uses BayesDel and SpliceAI.

BP6Supporting
BP6 · supporting

Expert panel ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel, ClinGen classified as Benign.

Recorded classification: Likely benign

ENIGMA BRCA1 and BRCA2 Specification v1.2 Table 3 final-classification framework

02The sources

Evidence at a glance

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

gnomAD v4.1
gnomAD v2.1
Population frequency
75 / 1,613,928 alleles

gnomAD v4.1: 75 / 1,613,928 alleles. Recorded AF 4.64705e-05. Recorded homozygote count 0.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 4.37487e-05; MAF= 0.00437%, 11/251436 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 7.91362e-05; MAF= 0.00791%, 9/113728 alleles, homozygotes = 0); grpmax FAF= 4.115e-05.

Applied · BS1 →
gnomAD v4.1 ↗gnomAD v2.1 ↗
No screenshot for this evidence
Computational predictions
Not recorded

No SpliceAI or REVEL score is recorded in the fields used for this tile.

Applied · BP4 →
Functional evidence
Statement recorded

OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Neutral; curated oncogenicity label: Likely Neutral.

Applied · BS3 → OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
Not assessed

No COSMIC evidence statement is recorded in this case.

Cancer Hotspots

This variant does not lie in a statistically significant hotspot.

Context only
COSMIC ↗Cancer Hotspots ↗
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: 4 met · 7 not met · 6 not assessed · 11 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Pathogenic
PVS1PS1PS2PS3PS4PM1PM2PM3PM4PM5PM6PP1PP2PP3PP4PP5
Benign
BA1BS1BS2BS3BS4BP1BP2BP3BP4BP5BP6BP7
Met Not met Not assessed Not applicable

The BRCA2 c.7759C>T (p.Leu2587Phe; p.L2587F) variant has been reported in ClinVar, where the ClinGen ENIGMA BRCA1/2 Variant Curation Expert Panel classifies it as benign.

This variant is present in gnomAD v2.1 and v4.1, with grpmax filter allele frequencies of 4.115e-05 and 4.535e-05, respectively; these values are above the ENIGMA BRCA2 BS1 Supporting threshold of 2.0e-05 and below the BS1 Strong threshold of 1.0e-04.

In calibrated functional studies curated by the ENIGMA BRCA2 specification, this variant showed protein function similar to benign control variants, supporting BS3 at Strong strength.

Computational evidence does not support a damaging effect under the ENIGMA BRCA2 rule because the BayesDel no-AF score is 0.147986 and the SpliceAI maximum delta score is 0.04, meeting BP4 thresholds for no predicted impact; REVEL is 0.73 but is not the operative ENIGMA BRCA2 threshold for this rule.

Met · 4

BS1 SupportingThis variant meets BS1 at Supporting strength because its filter allele frequency exceeds the ENIGMA BRCA2 BS1 Supporting threshold of 0.00002 but does not exceed the Strong threshold of 0.0001. In gnomAD v2.1, grpmax FAF is 4.115e-05, and in gnomAD v4.1, grpmax FAF is 4.535e-05. Details ▾Hide ▴
Rule
ENIGMA BRCA2 v1.2 BS1
Evidence considered
  • gnomAD v2.1 grpmax FAF 4.115e-05
  • gnomAD v4.1 grpmax FAF 4.535e-05
  • BS1 Supporting threshold >0.00002 and ≤0.0001
Sources
gnomad_v2 ↗gnomad_v4 ↗vcep_specifications_v1_2_2024_11_18vcep_appendices_v1_2_2024_11_18
BS3 StrongThis variant meets BS3 at Strong strength. In the ENIGMA BRCA2 curated functional assay table, two calibrated studies reported protein function similar to benign control variants, supporting a benign functional interpretation. Details ▾Hide ▴
Rule
ENIGMA BRCA2 v1.2 BS3
Evidence considered
  • Table 9 row for c.7759C>T / p.(Leu2587Phe) assigns BS3 Strong
  • Two calibrated studies cited by the VCEP table
Sources
vcep_specifications_table9_v1_2_2024_11_18vcep_specifications_v1_2_2024_11_18
BP4 SupportingThis variant meets BP4 at Supporting strength under the ENIGMA BRCA2 computational rule. Codon 2587 is within the BRCA2 DNA-binding domain, BayesDel no-AF is 0.147986, which is at or below the BP4 threshold of 0.18, and SpliceAI shows a maximum delta score of 0.04, which is at or below the BP4 threshold of 0.1. REVEL is 0.73, but the official ENIGMA BRCA2 rule for this criterion uses BayesDel and SpliceAI. Details ▾Hide ▴
Rule
ENIGMA BRCA2 v1.2 BP4
Evidence considered
  • Protein position 2587 is within the BRCA2 DNA-binding domain
  • BayesDel no-AF score 0.147986
  • SpliceAI max delta score 0.04
  • REVEL score 0.73
Sources
bayesdelspliceai ↗revelvcep_specifications_v1_2_2024_11_18vcep_appendices_v1_2_2024_11_18
BP6 SupportingExpert panel ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel, ClinGen classified as Benign. Details ▾Hide ▴
Rule
ENIGMA BRCA2 v1.2 BP6
Evidence considered
  • CSPEC/VCEP marked BP6 not applicable
  • ClinVar expert panel classification
Sources
vcep_specifications_v1_2_2024_11_18clinvar ↗

Not met · 7 · evaluated, threshold not reached

PS3 Available calibrated functional evidence does not support a damaging effect. In the ENIGMA BRCA2 curated functional table, this variant is assigned BS3_Strong rather than PS3 because published assays showed protein function similar to benign control variants. Details ▾Hide ▴
Rule
ENIGMA BRCA2 v1.2 PS3
Evidence considered
  • Table 9 row for c.7759C>T / p.(Leu2587Phe) assigns BS3 Strong
  • Two calibrated studies cited in the VCEP table
Sources
vcep_specifications_table9_v1_2_2024_11_18vcep_specifications_v1_2_2024_11_18PMID:29394989 ↗PMID:35736817 ↗
PM2 This variant is not absent from population controls. It is present in gnomAD v2.1 at 11/251436 alleles (AF 4.37487e-05) and in gnomAD v4.1 at 75/1613928 alleles (AF 4.64705e-05), so the ENIGMA BRCA2 PM2 absence criterion is not met. Details ▾Hide ▴
Rule
ENIGMA BRCA2 v1.2 PM2_Supporting requires absence from gnomAD controls.
Evidence considered
  • gnomAD v2.1 total AF 4.37487e-05
  • gnomAD v4.1 total AF 4.64705e-05
Sources
gnomad_v2 ↗gnomad_v4 ↗vcep_specifications_v1_2_2024_11_18vcep_appendices_v1_2_2024_11_18
PP3 Computational evidence does not meet the ENIGMA BRCA2 PP3 rule. This missense variant lies within the BRCA2 DNA-binding domain, but the BayesDel no-AF score is 0.147986, below the PP3 threshold of 0.30, and SpliceAI shows a maximum delta score of 0.04, below the splice threshold of 0.20. REVEL is 0.73, but the official ENIGMA BRCA2 rule for this criterion uses BayesDel and SpliceAI. Details ▾Hide ▴
Rule
ENIGMA BRCA2 v1.2 PP3 uses BayesDel no-AF ≥0.30 and/or SpliceAI ≥0.20 in the specified contexts.
Evidence considered
  • Protein position 2587 is within the BRCA2 DNA-binding domain
  • BayesDel no-AF score 0.147986
  • SpliceAI max delta score 0.04
  • REVEL score 0.73
Sources
bayesdelspliceai ↗revelvcep_specifications_v1_2_2024_11_18vcep_appendices_v1_2_2024_11_18
PP4 The BRCA2 clinical-history likelihood ratio for this variant is 0.5820637473 from 6 probands, which is below the ENIGMA BRCA2 PP4 Supporting threshold of 2.08. This value does not support pathogenic clinical-history enrichment. Details ▾Hide ▴
Rule
ENIGMA BRCA2 v1.2 PP4 uses multifactorial clinical-history LR thresholds.
Evidence considered
  • Li et al. BRCA2 clinical-history LR 0.5820637473
  • N probands 6
Sources
vcep_pmid_31853058_brca2_clinical_history_lrPMID:31853058 ↗vcep_specifications_v1_2_2024_11_18
BA1 Population frequency does not reach the ENIGMA BRCA2 BA1 threshold. The highest reviewed grpmax FAF is 4.535e-05 in gnomAD v4.1, which is below the BA1 threshold of 0.001. Details ▾Hide ▴
Rule
ENIGMA BRCA2 v1.2 BA1 requires FAF >0.001.
Evidence considered
  • gnomAD v2.1 grpmax FAF 4.115e-05
  • gnomAD v4.1 grpmax FAF 4.535e-05
Sources
gnomad_v2 ↗gnomad_v4 ↗vcep_specifications_v1_2_2024_11_18
BP1 This missense variant does not meet BP1 because codon 2587 is within the BRCA2 DNA-binding domain at amino acids 2481-3186, whereas the ENIGMA BRCA2 BP1 rule is for missense or silent variants outside a clinically important functional domain with no predicted splice effect. Details ▾Hide ▴
Rule
ENIGMA BRCA2 v1.2 BP1_Strong
Evidence considered
  • Protein position 2587 lies in the BRCA2 DNA-binding domain
  • SpliceAI max delta score 0.04
Sources
spliceai ↗vcep_specifications_v1_2_2024_11_18vcep_appendices_v1_2_2024_11_18
BP5 The BRCA2 clinical-history likelihood ratio for this variant is 0.5820637473 from 6 probands, which is above the ENIGMA BRCA2 BP5 Supporting threshold of 0.48. This value falls in the neutral zone and does not support a benign clinical-history criterion. Details ▾Hide ▴
Rule
ENIGMA BRCA2 v1.2 BP5 uses multifactorial clinical-history LR thresholds.
Evidence considered
  • Li et al. BRCA2 clinical-history LR 0.5820637473
  • N probands 6
Sources
vcep_pmid_31853058_brca2_clinical_history_lrPMID:31853058 ↗vcep_specifications_v1_2_2024_11_18

Not assessed · 6 · no assessment recorded

PS1 No qualifying evidence was identified showing that this variant has the same protein or splice consequence as a previously classified pathogenic or likely pathogenic BRCA2 variant under the ENIGMA BRCA2 rule. Details ▾Hide ▴
Rule
ENIGMA BRCA2 v1.2 PS1
Evidence considered
  • ENIGMA BRCA2 PS1 rule reviewed
  • ClinVar record reviewed
Still missing
  • No verified same-amino-acid or same-splice-effect reference variant was identified.
Sources
vcep_specifications_v1_2_2024_11_18clinvar ↗
PS4 No case-control study was identified showing a statistically significant enrichment of this variant in affected individuals compared with controls. Available multifactorial data were neutral rather than clearly supportive of pathogenic enrichment. Details ▾Hide ▴
Rule
ENIGMA BRCA2 v1.2 PS4 requires case-control enrichment with p≤0.05 and OR≥4.
Evidence considered
  • No qualifying case-control result identified
  • HUMU combined LR 1.046 and posterior probability 0.511 were not clearly supportive
Still missing
  • No verified odds ratio with p-value meeting the ENIGMA BRCA2 PS4 threshold was identified.
Sources
vcep_specifications_v1_2_2024_11_18vcep_humu_40_1557_s001clinvar ↗
PM3 No evidence was identified that this variant was observed with another BRCA2 variant in a patient with a phenotype consistent with BRCA2-related Fanconi anemia, so PM3 could not be evaluated. Details ▾Hide ▴
Rule
ENIGMA BRCA2 v1.2 PM3
Evidence considered
  • ENIGMA BRCA2 PM3 rule reviewed
Still missing
  • No qualifying recessive/Fanconi anemia case data were identified.
Sources
vcep_specifications_v1_2_2024_11_18
PP1 No quantitative segregation data were identified showing that this variant co-segregates with disease in affected family members, so PP1 could not be applied. Details ▾Hide ▴
Rule
ENIGMA BRCA2 v1.2 PP1
Evidence considered
  • ENIGMA BRCA2 PP1 rule reviewed
  • No segregation evidence identified in reviewed materials
Still missing
  • No pedigree-based segregation likelihood ratio was identified.
Sources
vcep_specifications_v1_2_2024_11_18clinvar ↗
BS2 No qualifying data were identified showing this variant in individuals without features of BRCA2-related Fanconi anemia in a way that would meet the ENIGMA BRCA2 BS2 point-based framework. Details ▾Hide ▴
Rule
ENIGMA BRCA2 v1.2 BS2
Evidence considered
  • ENIGMA BRCA2 BS2 rule reviewed
  • No homozygotes observed in gnomAD
Still missing
  • No BS2 point-based case data were identified.
Sources
vcep_specifications_v1_2_2024_11_18gnomad_v2 ↗gnomad_v4 ↗
BS4 No quantitative lack-of-segregation data were identified showing that this variant fails to track with disease in affected relatives, so BS4 could not be applied. Details ▾Hide ▴
Rule
ENIGMA BRCA2 v1.2 BS4
Evidence considered
  • ENIGMA BRCA2 BS4 rule reviewed
  • No qualifying non-segregation evidence identified
Still missing
  • No family-based non-segregation likelihood ratio was identified.
Sources
vcep_specifications_v1_2_2024_11_18clinvar ↗vcep_supplementarytables_v1_2_2024_11_18vcep_humu_40_1557_s001
Not applicable · 11· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/AThis variant is a missense substitution, p.(Leu2587Phe), and available data do not show a predicted or demonstrated loss-of-function splicing effect. SpliceAI shows a maximum delta score of 0.04, below the ENIGMA BRCA2 splice-prediction thresholds used for PVS1-related consideration. Details ▾Hide ▴
Rule
ENIGMA BRCA2 v1.2 PVS1 applies to null variants or qualifying RNA-only loss-of-function evidence.
Evidence considered
  • Missense consequence p.(Leu2587Phe)
  • Generic PVS1 scaffold did not place this variant in a null-variant bucket
  • SpliceAI max delta score 0.04
Still missing
  • No variant-specific RNA assay demonstrating an abnormal transcript was identified.
Sources
pvs1_gene_contextpvs1_variant_assessmentspliceai ↗vcep_specifications_v1_2_2024_11_18pvs1_generic_framework ↗
PS2 N/AThis criterion is not applicable in the ENIGMA BRCA2 specification for this review context. Details ▾Hide ▴
Rule
ENIGMA BRCA2 v1.2 PS2
Evidence considered
  • CSPEC/VCEP marked PS2 not applicable
Sources
vcep_specifications_v1_2_2024_11_18
PM1 N/AAlthough codon 2587 lies within the BRCA2 DNA-binding region, the ENIGMA BRCA2 specification marks PM1 as not applicable for this framework. Details ▾Hide ▴
Rule
ENIGMA BRCA2 v1.2 PM1
Evidence considered
  • CSPEC/VCEP marked PM1 not applicable
Sources
vcep_specifications_v1_2_2024_11_18vcep_appendices_v1_2_2024_11_18
PM4 N/AThis criterion is not applicable in the ENIGMA BRCA2 specification for this review context. Details ▾Hide ▴
Rule
ENIGMA BRCA2 v1.2 PM4
Evidence considered
  • CSPEC/VCEP marked PM4 not applicable
Sources
vcep_specifications_v1_2_2024_11_18
PM5 N/AUnder the ENIGMA BRCA2 specification, the reviewed PM5 rule is for protein-truncating variants in eligible exons. This variant is a missense substitution and does not meet that rule context. Details ▾Hide ▴
Rule
ENIGMA BRCA2 v1.2 PM5_PTC
Evidence considered
  • Missense consequence p.(Leu2587Phe)
  • Table 4 reviewed for PTC-only PM5 context
Sources
vcep_specifications_v1_2_2024_11_18vcep_specifications_table4_v1_2_2024_11_18vcep_appendices_v1_2_2024_11_18
PM6 N/AThis criterion is not applicable in the ENIGMA BRCA2 specification for this review context. Details ▾Hide ▴
Rule
ENIGMA BRCA2 v1.2 PM6
Evidence considered
  • CSPEC/VCEP marked PM6 not applicable
Sources
vcep_specifications_v1_2_2024_11_18
PP2 N/AThis criterion is not applicable in the ENIGMA BRCA2 specification for this review context. Details ▾Hide ▴
Rule
ENIGMA BRCA2 v1.2 PP2
Evidence considered
  • CSPEC/VCEP marked PP2 not applicable
Sources
vcep_specifications_v1_2_2024_11_18
PP5 N/AThis criterion is not applicable in the ENIGMA BRCA2 specification for this review context. Details ▾Hide ▴
Rule
ENIGMA BRCA2 v1.2 PP5
Evidence considered
  • CSPEC/VCEP marked PP5 not applicable
Sources
vcep_specifications_v1_2_2024_11_18
BP2 N/AThis criterion is not applicable in the ENIGMA BRCA2 specification for this review context. Details ▾Hide ▴
Rule
ENIGMA BRCA2 v1.2 BP2
Evidence considered
  • CSPEC/VCEP marked BP2 not applicable
Sources
vcep_specifications_v1_2_2024_11_18
BP3 N/AThis criterion is not applicable in the ENIGMA BRCA2 specification for this review context. Details ▾Hide ▴
Rule
ENIGMA BRCA2 v1.2 BP3
Evidence considered
  • CSPEC/VCEP marked BP3 not applicable
Sources
vcep_specifications_v1_2_2024_11_18
BP7 N/AThis is a missense variant in the BRCA2 DNA-binding domain, and no qualifying RNA-only benign evidence was identified for BP7 application. Details ▾Hide ▴
Rule
ENIGMA BRCA2 v1.2 BP7
Evidence considered
  • Missense consequence p.(Leu2587Phe)
  • SpliceAI max delta score 0.04
Still missing
  • No variant-specific benign RNA assay was identified.
Sources
spliceai ↗vcep_specifications_v1_2_2024_11_18vcep_pmid_22505045_houdayer_2012_hummutat

Identifiers

Gene
BRCA2
Transcript
NM_000059.3
Coding (HGVS c.)
NM_000059.3:c.7759C>T
Protein (HGVS p.)
NP_000050.2:p.(Leu2587Phe)
GRCh38
chr13:32357883 C>T
GRCh37
chr13:32932020 C>T

Gene diagram

Every interpreted variant in BRCA2, mapped onto the exon structure of NM_000059.3. Select a row to find it on the plot.

BRCA2NM_000059.3
Fetching transcript structure from UCSC…
gnomAD v4.1 75 / 1,613,928 alleles AF 4.65e-05 · 0 homozygotes · FAF 4.53e-05
gnomAD v2.1 11 / 251,436 alleles AF 4.37e-05 · 0 homozygotes · FAF 4.11e-05

By genetic ancestry

gnomAD v4.1

AF 4.6e-05 · 75 / 1,613,928 alleles · 0 hom · FAF 4.5e-05
Remaining individuals5 / 62,478 8e-05
European (non-Finnish)67 / 1,180,010 5.7e-05
Admixed American2 / 59,996 3.3e-05
European (Finnish)1 / 64,016 1.6e-05
0 alternate alleles recorded in 6 other groups: Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish, African/African American.

gnomAD v2.1

AF 4.4e-05 · 11 / 251,436 alleles · 0 hom · FAF 4.1e-05
European (non-Finnish)9 / 113,728 7.9e-05
Admixed American2 / 34,590 5.8e-05
0 alternate alleles recorded in 6 other groups: African/African American, Ashkenazi Jewish, East Asian, European (Finnish), Remaining individuals, South Asian.

Statements

gnomAD v4.1

This variant is present in gnomAD v4.1 (AF= 4.64705e-05; MAF= 0.00465%, 75/1613928 alleles, homozygotes = 0) and has highest observed frequency in the Remaining individuals population (AF= 8.00282e-05; MAF= 0.00800%, 5/62478 alleles, homozygotes = 0); grpmax FAF= 4.535e-05.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 4.37487e-05; MAF= 0.00437%, 11/251436 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 7.91362e-05; MAF= 0.00791%, 9/113728 alleles, homozygotes = 0); grpmax FAF= 4.115e-05.

Other predictors

REVEL
Not available
BayesDel
Not available

How the predictions were used

BP4 SupportingThis variant meets BP4 at Supporting strength under the ENIGMA BRCA2 computational rule. Codon 2587 is within the BRCA2 DNA-binding domain, BayesDel no-AF is 0.147986, which is at or below the BP4 threshold of 0.18, and SpliceAI shows a maximum delta score of 0.04, which is at or below the BP4 threshold of 0.1. REVEL is 0.73, but the official ENIGMA BRCA2 rule for this criterion uses BayesDel and SpliceAI. Details ▾Hide ▴
Rule
ENIGMA BRCA2 v1.2 BP4
Evidence considered
  • Protein position 2587 is within the BRCA2 DNA-binding domain
  • BayesDel no-AF score 0.147986
  • SpliceAI max delta score 0.04
  • REVEL score 0.73
Sources
bayesdelspliceai ↗revelvcep_specifications_v1_2_2024_11_18vcep_appendices_v1_2_2024_11_18
PP3 Computational evidence does not meet the ENIGMA BRCA2 PP3 rule. This missense variant lies within the BRCA2 DNA-binding domain, but the BayesDel no-AF score is 0.147986, below the PP3 threshold of 0.30, and SpliceAI shows a maximum delta score of 0.04, below the splice threshold of 0.20. REVEL is 0.73, but the official ENIGMA BRCA2 rule for this criterion uses BayesDel and SpliceAI. Details ▾Hide ▴
Rule
ENIGMA BRCA2 v1.2 PP3 uses BayesDel no-AF ≥0.30 and/or SpliceAI ≥0.20 in the specified contexts.
Evidence considered
  • Protein position 2587 is within the BRCA2 DNA-binding domain
  • BayesDel no-AF score 0.147986
  • SpliceAI max delta score 0.04
  • REVEL score 0.73
Sources
bayesdelspliceai ↗revelvcep_specifications_v1_2_2024_11_18vcep_appendices_v1_2_2024_11_18
BP7 N/AThis is a missense variant in the BRCA2 DNA-binding domain, and no qualifying RNA-only benign evidence was identified for BP7 application. Details ▾Hide ▴
Rule
ENIGMA BRCA2 v1.2 BP7
Evidence considered
  • Missense consequence p.(Leu2587Phe)
  • SpliceAI max delta score 0.04
Still missing
  • No variant-specific benign RNA assay was identified.
Sources
spliceai ↗vcep_specifications_v1_2_2024_11_18vcep_pmid_22505045_houdayer_2012_hummutat

Statement

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.04). REVEL score = 0.73. BayesDel score = 0.147986.

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.

gnomAD v4.1 75 / 1,613,928 recorded alleles Open source ↗
gnomAD v2.1 Captured gnomAD v2.1 source record Open source ↗
SpliceAI Lookup Captured SpliceAI source record Open source ↗
ClinVar Captured ClinVar source record Open source ↗
COSMIC Captured COSMIC source record Open source ↗
Cancer hotspots Captured Cancer Hotspots source record Open source ↗
OncoKB Captured OncoKB source record Open source ↗
ClinGen CSpec Captured ClinGen CSpec source record Open source ↗

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

This variant is present in gnomAD v4.1 (AF= 4.64705e-05; MAF= 0.00465%, 75/1613928 alleles, homozygotes = 0) and has highest observed frequency in the Remaining individuals population (AF= 8.00282e-05; MAF= 0.00800%, 5/62478 alleles, homozygotes = 0); grpmax FAF= 4.535e-05.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 4.37487e-05; MAF= 0.00437%, 11/251436 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 7.91362e-05; MAF= 0.00791%, 9/113728 alleles, homozygotes = 0); grpmax FAF= 4.115e-05.

ClinVar

This variant has been reported in ClinVar as Uncertain significance (8 clinical laboratories) and as Likely benign (6 clinical laboratories) and as Benign (2 clinical laboratories) and as Likely Benign (1 clinical laboratory) and as Likely pathogenic (1 clinical laboratory) and as Benign by ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel, ClinGen (expert panel).

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.04). REVEL score = 0.73. BayesDel score = 0.147986.

Functional

OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Neutral; curated oncogenicity label: Likely Neutral.

Somatic

This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).

Cancer Hotspots

This variant does not lie in a statistically significant hotspot.