About BRCA2
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
BRCA2 c.3111A>G, p.(Gln1037=)
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.
Words with a dotted underline have a short definition. Hover or tap them.
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: 1
Pathogenic criteria applied · 0
No pathogenic criterion marked as applied in the recorded assessment.
Benign criteria applied · 1
BP1Strong
BP1 · strong
This is a silent/synonymous BRCA2 variant, p.(Gln1037=)/p.(Q1037=), located outside the BRCA2 clinically important domains (PALB2-binding aa 10-40 and DNA-binding aa 2481-3186). SpliceAI predicts no splice effect with max delta 0.00. Under the BRCA2 ENIGMA specification, BP1_Strong applies to silent variants outside clinically important domains when no splicing is predicted.
Recorded classification: Likely benign
BRCA2 ENIGMA/ClinGen VCEP v1.2 adapted ACMG/AMP framework. BP1_Strong is met, and the specification's Table 3 allows Likely Benign from one Strong benign code when multiple evidence types contribute to that code; the specification explicitly cites BP1_Strong as such an example.
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
8 / 1,612,374 alleles
gnomAD v4.1: 8 / 1,612,374 alleles. Recorded AF 4.96163e-06. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 4.00702e-06; MAF= 0.00040%, 1/249562 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 6.18123e-05; MAF= 0.00618%, 1/16178 alleles, homozygotes = 0).
No listed criterion applied
No screenshot for this evidence
Computational predictions
Not recorded
No SpliceAI or REVEL score is recorded in the fields used for this tile.
No listed criterion applied
ClinVar submissions
Not recorded
A ClinVar laboratory submission summary was not recorded.
Context only
ClinVar ↗
Functional evidence
Statement recorded
OncoKB oncogenicity for this specific variant: Unknown Oncogenic Effect (variant has not been individually curated).
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
Not assessed
No COSMIC evidence statement is recorded in this case.
Context only
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: 1 met · 15 not met · 0 not assessed · 12 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.3111A>G normalizes to the synonymous BRCA2 protein consequence p.(Gln1037=) / p.(Q1037=).
Q1037 is outside the BRCA2 clinically important domains defined by the specification (PALB2-binding aa 10-40 and DNA-binding aa 2481-3186).
SpliceAI predicts no significant splice impact for this variant, with max delta score 0.00, satisfying the no-splicing-predicted part of BP1_Strong.
The BRCA2 ENIGMA specification states to apply BP1_Strong for silent variants outside clinically important domains with SpliceAI ≤0.1, and its Table 3 states Likely Benign can be assigned from one Strong benign code when multiple evidence types contribute; BP1_Strong is given as an explicit example.
Population data do not support BA1 or BS1, and the variant is not absent from controls, so PM2 is also not met; these findings do not overturn the BP1_Strong-based Likely Benign classification.
No criteria match.
Met · 1
BP1 StrongThis is a silent/synonymous BRCA2 variant, p.(Gln1037=)/p.(Q1037=), located outside the BRCA2 clinically important domains (PALB2-binding aa 10-40 and DNA-binding aa 2481-3186). SpliceAI predicts no splice effect with max delta 0.00. Under the BRCA2 ENIGMA specification, BP1_Strong applies to silent variants outside clinically important domains when no splicing is predicted. Details ▾Hide ▴
Rule
Apply BP1_Strong for silent substitution, missense or in-frame insertion/deletion outside a clinically important functional domain and no splicing predicted (SpliceAI ≤0.1).
Evidence considered
- Normalized consequence: NP_000050.3:p.(Gln1037=) / p.(Q1037=).
- Q1037 lies outside aa 10-40 and aa 2481-3186 BRCA2 clinically important domains.
- SpliceAI max delta score = 0.00.
Sources
Not met · 15 · evaluated, threshold not reached
PS1 No same-amino-acid pathogenic comparator or same predicted splice consequence pathogenic comparator was identified in the reviewed workspace materials. Details ▾Hide ▴
Rule
Apply PS1 only when the variant has the same established pathogenic protein or splice consequence as a previously classified pathogenic/likely pathogenic variant.
Evidence considered
- ClinVar scrape found no result for this variant.
- No supporting PS1 comparator evidence was present in the assembled workspace.
Sources
PS3 No variant-specific damaging functional assay assignment was identified in Specifications Table 9 or other reviewed VCEP materials. Details ▾Hide ▴
Rule
PS3 requires well-established damaging functional evidence.
Evidence considered
- No c.3111A>G / p.(Q1037=) entry was found in the curated functional assay table reviewed from the BRCA2 VCEP folder.
Sources
vcep_s_p_e_c_i_f_i_c_a_t_i_o_n_s___t_a_b_l_e_9___v_1___2___2_0_2_4___1_1___1_8
PS4 No case-control enrichment evidence for this specific variant was identified in the workspace, and the variant is absent from ClinVar submissions that might have pointed to such data. Details ▾Hide ▴
Rule
PS4 requires significant enrichment in affected individuals versus controls.
Evidence considered
- ClinVar scrape found no result for this variant.
- No variant-specific PS4-supporting lookup was identified in the reviewed VCEP materials.
Sources
clinvar ↗vcep_s_u_p_p_l_e_m_e_n_t_a_r_y_t_a_b_l_e_s___v_1___2___2_0_2_4___1_1___1_8
PM2 PM2_Supporting requires absence from gnomAD controls. This variant is present in both gnomAD v2.1 and v4.1, so PM2 is not met. Details ▾Hide ▴
Rule
BRCA2 PM2 is Supporting only when absent from outbred controls with adequate coverage.
Evidence considered
- gnomAD v2.1: 1/249562 alleles, AF 4.00702e-06.
- gnomAD v4.1: 8/1612374 alleles, AF 4.96163e-06; grpmax FAF 4.089e-05.
Sources
PP1 No quantitative segregation data were present in the workspace. Details ▾Hide ▴
Rule
PP1 requires quantitative co-segregation evidence.
Evidence considered
- No pedigree-based LR or segregation dataset was assembled for this case.
Sources
PP3 PP3 is not met because SpliceAI shows no predicted splice impact (max delta 0.00), and this synonymous variant is outside the clinically important domains where missense-domain PP3 logic would apply. Details ▾Hide ▴
Rule
BRCA2 PP3 for silent variants requires predicted splicing impact (SpliceAI ≥0.2).
Evidence considered
- SpliceAI DS_AG/DS_AL/DS_DG/DS_DL all 0.0; max delta score 0.00.
- Protein consequence is synonymous p.(Q1037=).
Sources
PP4 No multifactorial likelihood clinical data supporting phenotype-specific enrichment were present in the workspace. Details ▾Hide ▴
Rule
BRCA2 PP4 is reserved for multifactorial likelihood clinical data.
Evidence considered
- No BRCA2 multifactorial LR for this variant was assembled in the reviewed case materials.
Sources
BA1 The observed population frequency is far below the BRCA2 BA1 threshold. Details ▾Hide ▴
Rule
BRCA2 BA1 requires FAF >0.1% in a non-founder population.
Evidence considered
- gnomAD v4.1 grpmax FAF is 4.089e-05, well below the BA1 threshold of >0.001.
- gnomAD v2.1 frequency is also far below BA1.
Sources
BS1 The observed population frequency is below both BRCA2 BS1 thresholds. Details ▾Hide ▴
Rule
BRCA2 BS1 requires FAF >0.0001 for Strong or >0.00002 to ≤0.0001 for Supporting in non-founder populations.
Evidence considered
- gnomAD v4.1 grpmax FAF is 4.089e-05, below the Strong threshold >0.0001 and above neither tier conclusively for a non-founder population.
- gnomAD v2.1 has no qualifying FAF above threshold.
Sources
BS2 No adult biallelic or phenotype-negative observational dataset relevant to BRCA2 BS2 was present in the workspace. Details ▾Hide ▴
Rule
BRCA2 BS2 requires phenotype-negative observations scored per specification Table 8.
Evidence considered
- No BS2 point-based evidence was assembled.
Sources
BS3 No variant-specific benign protein functional assay assignment was identified in the reviewed BRCA2 functional table. Details ▾Hide ▴
Rule
BS3 requires well-established functional studies showing no damaging effect on protein function.
Evidence considered
- No c.3111A>G / p.(Q1037=) entry was found in Specifications Table 9.
Sources
vcep_s_p_e_c_i_f_i_c_a_t_i_o_n_s___t_a_b_l_e_9___v_1___2___2_0_2_4___1_1___1_8
BS4 No quantitative lack-of-segregation evidence was present in the workspace. Details ▾Hide ▴
Rule
BS4 requires quantitative non-segregation evidence.
Evidence considered
- No segregation LR against pathogenicity was assembled for this case.
Sources
BP4 For silent variants, BRCA2 BP4 applies only inside a clinically important functional domain with no predicted splice impact. This synonymous variant is outside those domains, so BP4 is not the correct benign bioinformatic code. Details ▾Hide ▴
Rule
Silent variant inside a clinically important domain, if no predicted impact via splicing (SpliceAI ≤0.1).
Evidence considered
- Q1037 is outside BRCA2 aa 10-40 and aa 2481-3186 clinically important domains.
- SpliceAI max delta score = 0.00.
Sources
BP5 No multifactorial likelihood clinical data arguing against pathogenicity were assembled for this specific variant. Details ▾Hide ▴
Rule
BRCA2 BP5 is used only to capture combined LR against pathogenicity from multifactorial clinical data.
Evidence considered
- No BP5-relevant LR data were present in the workspace.
Sources
BP7 BRCA2 BP7 for silent variants is used in addition to BP4 for silent variants inside a clinically important domain, or as BP7_Strong with qualifying RNA assay data. This variant is outside the defined domains and no RNA assay was identified, so BP7 is not met. Details ▾Hide ▴
Rule
Apply BP7 for silent variant inside a clinically important domain if BP4 is met; BP7_Strong may be used for qualifying mRNA-only functional evidence.
Evidence considered
- SpliceAI max delta score = 0.00.
- No variant-specific RNA assay evidence was identified in the reviewed workspace or VCEP materials.
Sources
Not applicable · 12· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ASynonymous exon 11 variant p.(Gln1037=)/p.(Q1037=) with no evidence in the workspace for an RNA assay showing loss-of-function transcript impact; BRCA2 PVS1 is for null variants or qualifying mRNA assay evidence. Details ▾Hide ▴
Rule
BRCA2 ENIGMA PVS1 applies to null variants or qualifying mRNA assay evidence, not an uncomplicated synonymous substitution without splice impact.
Evidence considered
- NM_000059.4:c.3111A>G normalizes to NP_000050.3:p.(Gln1037=) / p.(Q1037=).
- SpliceAI max delta score is 0.00, so no predicted spliceogenic effect was identified.
Sources
PS2 N/ANo de novo case data are present, and the BRCA2 specification marks PS2 as not applicable. Details ▾Hide ▴
PM1 N/AThe BRCA2 VCEP marks PM1 as not applicable in this specification. Details ▾Hide ▴
PM3 N/ANo Fanconi anemia phenotype or in-trans co-occurrence evidence is present in the workspace. Details ▾Hide ▴
Rule
BRCA2 PM3 is used for BRCA2-related Fanconi anemia context with co-occurring variants.
Evidence considered
- No PM3-relevant case data were assembled in the workspace.
Sources
PM4 N/AThe BRCA2 VCEP marks PM4 as not applicable. Details ▾Hide ▴
PM5 N/AThis is not a protein-terminating variant and not a missense substitution requiring PM5 logic. Details ▾Hide ▴
Rule
BRCA2 PM5 in this specification addresses PTC context via Table 4, which does not apply here.
Evidence considered
- Variant is synonymous, not PTC or missense.
Sources
cspec ↗vcep_s_p_e_c_i_f_i_c_a_t_i_o_n_s___t_a_b_l_e_4___v_1___2___2_0_2_4___1_1___1_8
PM6 N/AThe BRCA2 VCEP marks PM6 as not applicable. Details ▾Hide ▴
PP2 N/AThe BRCA2 VCEP marks PP2 as not applicable. Details ▾Hide ▴
PP5 N/AThe BRCA2 VCEP marks PP5 as not applicable. Details ▾Hide ▴
BP2 N/AThe BRCA2 VCEP marks BP2 as not applicable except in the BS2 context, and no such evidence is present. Details ▾Hide ▴
BP3 N/AThe BRCA2 VCEP marks BP3 as not applicable. Details ▾Hide ▴
BP6 N/AThe BRCA2 VCEP marks BP6 as not applicable. Details ▾Hide ▴
Identifiers
- Gene
- BRCA2
- Transcript
- NM_000059.4
- Coding (HGVS c.)
- NM_000059.4:c.3111A>G
- Protein (HGVS p.)
- NP_000050.3:p.(Gln1037=)
- GRCh38
- chr13:32337466 A>G
- GRCh37
- chr13:32911603 A>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…
Exons
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Transcript span
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Strand
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Variants mapped
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Source
UCSC ncbiRefSeqCurated
All variants in BRCA2
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Select a row to find it on the plot; use the link to open its page.
| Protein | Location | Classification | Link |
|---|
gnomAD v4.1
8 / 1,612,374 alleles
AF 4.96e-06 · 0 homozygotes · FAF 4.09e-05
gnomAD v2.1
1 / 249,562 alleles
AF 4.01e-06 · 0 homozygotes
By genetic ancestry
gnomAD v4.1
AF 5e-06 · 8 / 1,612,374 alleles · 0 hom · FAF 4.1e-05
| Middle Eastern1 / 6,068 | 0.00016 |
| African/African American5 / 74,872 | 6.7e-05 |
| East Asian1 / 44,848 | 2.2e-05 |
| European (non-Finnish)1 / 1,179,106 | 8.5e-07 |
0 alternate alleles recorded in 6 other groups: Remaining individuals, Admixed American, European (Finnish), South Asian, Ashkenazi Jewish, Amish.
gnomAD v2.1
AF 4e-06 · 1 / 249,562 alleles · 0 hom
| African/African American1 / 16,178 | 6.2e-05 |
0 alternate alleles recorded in 7 other groups: Admixed American, Ashkenazi Jewish, East Asian, European (Finnish), European (non-Finnish), Remaining individuals, South Asian.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 4.96163e-06; MAF= 0.00050%, 8/1612374 alleles, homozygotes = 0) and has highest observed frequency in the Middle Eastern population (AF= 0.000164799; MAF= 0.01648%, 1/6068 alleles, homozygotes = 0); grpmax FAF= 4.089e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 4.00702e-06; MAF= 0.00040%, 1/249562 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 6.18123e-05; MAF= 0.00618%, 1/16178 alleles, homozygotes = 0).
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
PP3 PP3 is not met because SpliceAI shows no predicted splice impact (max delta 0.00), and this synonymous variant is outside the clinically important domains where missense-domain PP3 logic would apply. Details ▾Hide ▴
Rule
BRCA2 PP3 for silent variants requires predicted splicing impact (SpliceAI ≥0.2).
Evidence considered
- SpliceAI DS_AG/DS_AL/DS_DG/DS_DL all 0.0; max delta score 0.00.
- Protein consequence is synonymous p.(Q1037=).
Sources
BP4 For silent variants, BRCA2 BP4 applies only inside a clinically important functional domain with no predicted splice impact. This synonymous variant is outside those domains, so BP4 is not the correct benign bioinformatic code. Details ▾Hide ▴
Rule
Silent variant inside a clinically important domain, if no predicted impact via splicing (SpliceAI ≤0.1).
Evidence considered
- Q1037 is outside BRCA2 aa 10-40 and aa 2481-3186 clinically important domains.
- SpliceAI max delta score = 0.00.
Sources
BP7 BRCA2 BP7 for silent variants is used in addition to BP4 for silent variants inside a clinically important domain, or as BP7_Strong with qualifying RNA assay data. This variant is outside the defined domains and no RNA assay was identified, so BP7 is not met. Details ▾Hide ▴
Rule
Apply BP7 for silent variant inside a clinically important domain if BP4 is met; BP7_Strong may be used for qualifying mRNA-only functional evidence.
Evidence considered
- SpliceAI max delta score = 0.00.
- No variant-specific RNA assay evidence was identified in the reviewed workspace or VCEP materials.
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.
gnomAD v4.1
8 / 1,612,374 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
Cancer hotspots
Captured Cancer Hotspots source record
OncoKB
Captured OncoKB source record
Open source ↗
ClinGen CSpec
Captured ClinGen CSpec source record
Open source ↗
All source links
- ClinGen CSpec ↗cspec.genome.network/cspec/ui/svi/doc/1535438831
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/4215832/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/13-32911603-A-G?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr13-32337466-A-G?dataset=gn…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000059.4%3Ac.3111…
- OncoKB ↗www.oncokb.org/gene/BRCA2/Q1037=
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= 4.96163e-06; MAF= 0.00050%, 8/1612374 alleles, homozygotes = 0) and has highest observed frequency in the Middle Eastern population (AF= 0.000164799; MAF= 0.01648%, 1/6068 alleles, homozygotes = 0); grpmax FAF= 4.089e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 4.00702e-06; MAF= 0.00040%, 1/249562 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 6.18123e-05; MAF= 0.00618%, 1/16178 alleles, homozygotes = 0).
ClinVar
This variant is absent from ClinVar.
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
Functional
OncoKB oncogenicity for this specific variant: Unknown Oncogenic Effect (variant has not been individually curated).
Somatic
This variant has not previously been reported in somatic cancers (COSMIC).