About BRCA2
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
BRCA2 c.8386C>T, p.(Pro2796Ser)
Classification
Uncertain significance
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is uncertain. Select a step to read what it means.
Uncertain.The recorded classification is uncertain significance.
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. 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
BP5Supporting
BP5 · supporting
ENIGMA BP5 Supporting applies when the combined likelihood ratio from multifactorial likelihood clinical data is ≤ 0.48:1. The combined LR from Parsons et al. 2019 (PMID:31131967) multifactorial analysis for NM_000059.4:c.8386C>T is 0.123, with a posterior probability of pathogenicity of 0.0038 and IARC class 2 (Likely Benign). The combined LR of 0.123 supports BP5 at Supporting strength. The combined LR incorporates co-occurrence, family history, pathology, and case-control likelihood components.
Recorded classification: Uncertain significance
ENIGMA BRCA2 v1.2 Table 3 combination rules applied. Only BP5 met at Supporting benign strength (Parsons et al. 2019 combined LR=0.123). No Likely Benign combination rule matches: all Likely Benign rules require either 2x Supporting (Benign) or 1x Strong (Benign) + 1x Supporting/Moderate (Benign). No pathogenic criteria met. ENIGMA point system yields -1 point, which maps to Uncertain Significance range (-1 to 5). Variant defaults to VUS.
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
28 / 1,613,960 alleles
gnomAD v4.1: 28 / 1,613,960 alleles. Recorded AF 1.73486e-05. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.59082e-05; MAF= 0.00159%, 4/251442 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 3.51716e-05; MAF= 0.00352%, 4/113728 alleles, homozygotes = 0); grpmax FAF= 1.122e-05.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
No listed criterion applied
SpliceAI score
0.160 maximum delta
Recorded SpliceAI maximum delta score: 0.160. Refer to the recorded PP3/BP4 rationale for interpretation.
No listed criterion applied
SpliceAI ↗
ClinVar submissions
12 reported laboratory submissions
7 Uncertain significance · 4 Likely benign · 1 Benign. ClinVar API review status: criteria provided, conflicting classifications.
Context only
ClinVar ↗
Functional evidence
Statement recorded
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. BRCA2, a tumor suppressor involved in the DNA damage response, is mutated in various cancer types.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
No matching record reported
This variant has not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under ClinGen BRCA2 VCEP v1.2, with the data and sources behind each one.
29 criteria with recorded statuses: 1 met · 11 not met · 4 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
No criteria match.
Met · 1
BP5 SupportingENIGMA BP5 Supporting applies when the combined likelihood ratio from multifactorial likelihood clinical data is ≤ 0.48:1. The combined LR from Parsons et al. 2019 (PMID:31131967) multifactorial analysis for NM_000059.4:c.8386C>T is 0.123, with a posterior probability of pathogenicity of 0.0038 and IARC class 2 (Likely Benign). The combined LR of 0.123 supports BP5 at Supporting strength. The combined LR incorporates co-occurrence, family history, pathology, and case-control likelihood components. Details ▾Hide ▴
Evidence considered
- ENIGMA BP5 Supporting: combined LR ≤ 0.48
- Parsons et al. 2019 SuppT1: Combined LR = 0.123 (≤ 0.48 → BP5 Supporting)
- Posterior probability of pathogenicity: 0.0038
- IARC class: 2 (Likely Benign)
- Li et al. 2020 clinical history LR: variant not present (no additional BP5 data)
Sources
Not met · 11 · evaluated, threshold not reached
PS1 No previously classified pathogenic missense variant at codon 2796 has been identified. ENIGMA PS1 requires a same-amino-acid change as a previously classified pathogenic variant, or same predicted splicing impact as a classified pathogenic variant. No comparator variant at this codon was found. Details ▾Hide ▴
Evidence considered
- ENIGMA BRCA2 v1.2 PS1 rule requires a previously classified pathogenic variant with same amino acid change
- No pathogenic variant at codon 2796 was identified in ClinVar or VCEP materials
Still missing
- No same-codon comparator variants available for PS1 assessment
Sources
PS3 NM_000059.4:c.8386C>T is not listed in ENIGMA Specifications Table 9 (curated BRCA2 functional assay results). No calibrated mammalian functional studies demonstrating a damaging effect on protein function are available for this variant. OncoKB reports Unknown Oncogenic Effect with no variant-specific functional evidence. Details ▾Hide ▴
Evidence considered
- ENIGMA Table 9: variant not listed — no pre-assigned PS3/BS3 code
- SuppT4: no functional assay data for c.8386C>T
- OncoKB: Unknown Oncogenic Effect
- no variant-specific functional evidence
Still missing
- No calibrated functional studies for this variant
Sources
PM2 Under ENIGMA BRCA2 v1.2, PM2 (Supporting only) requires absence from controls in gnomAD outbred populations. NM_000059.4:c.8386C>T is present in gnomAD v2.1 (4/251,442 alleles; grpmax FAF = 1.122e-05) and gnomAD v4.1 (28/1,613,960 alleles). The variant is not absent from population controls. Details ▾Hide ▴
Evidence considered
- ENIGMA PM2 (Supporting) requires absence from gnomAD outbred populations
- gnomAD v2.1: 4 alleles observed (AF = 1.59e-05)
- mostly European non-Finnish
- gnomAD v4.1: 28 alleles observed (AF = 1.73e-05)
Sources
PP3 Although p.Pro2796Ser lies within the BRCA2 DNA binding domain (aa 2481-3186), neither ENIGMA PP3 condition is satisfied: BayesDel no-AF score is -0.202329 (threshold ≥ 0.30 not met) and SpliceAI max delta is 0.16 (threshold ≥ 0.2 not met). No predicted impact on protein function or splicing by ENIGMA bioinformatic thresholds. Details ▾Hide ▴
Evidence considered
- ENIGMA PP3 requires BayesDel no-AF ≥ 0.30 OR SpliceAI ≥ 0.2 for missense inside functional domain
- BayesDel no-AF: -0.202329 (< 0.30 threshold)
- SpliceAI max delta: 0.16 (< 0.2 threshold)
- REVEL: 0.328 (informational only
- ENIGMA does not use REVEL for PP3)
Sources
PP4 ENIGMA PP4 requires a combined LR ≥ 2.08:1 toward pathogenicity from multifactorial likelihood clinical data. The combined multifactorial LR from Parsons et al. 2019 (PMID:31131967) for NM_000059.4:c.8386C>T is 0.123, which is in the benign direction and well below the PP4 Supporting threshold. The variant is not present in the Li et al. 2020 clinical history LR dataset. Details ▾Hide ▴
Evidence considered
- ENIGMA PP4 requires combined LR ≥ 2.08:1
- Parsons et al. 2019 SuppT1: Combined LR = 0.123 (benign direction)
- Li et al. 2020 clinical history LR: variant not present in dataset
Sources
BA1 ENIGMA BA1 (Stand Alone) requires filter allele frequency (FAF) > 0.1% (0.001) in gnomAD. The grpmax FAF for NM_000059.4:c.8386C>T is 1.122e-05 (0.00112%), far below the BA1 threshold. The variant is too rare in population databases to meet BA1. Details ▾Hide ▴
Evidence considered
- ENIGMA BA1 requires FAF > 0.001 (0.1%)
- gnomAD v2.1 grpmax FAF: 1.122e-05 (0.00112%)
Sources
BS1 ENIGMA BS1 Strong requires FAF > 0.01% (0.0001); BS1 Supporting requires FAF > 0.002% (0.00002). The grpmax FAF for NM_000059.4:c.8386C>T is 1.122e-05 (0.00112%), which is below even the Supporting threshold of 0.002%. The variant is too rare in population databases to meet BS1 at any strength. Details ▾Hide ▴
Evidence considered
- ENIGMA BS1 Strong: FAF > 0.0001
- Supporting: FAF > 0.00002
- gnomAD v2.1 grpmax FAF: 1.122e-05 (0.001122%
- below 0.002% threshold)
Sources
BS3 NM_000059.4:c.8386C>T is not listed in ENIGMA Specifications Table 9 (curated functional assay results). No calibrated mammalian functional studies demonstrating no damaging effect on protein function are available. The Houdayer et al. 2012 (PMID:22505045) splicing assay showed no splicing aberration, but this is mRNA-level evidence only and does not satisfy BS3, which requires protein-level or combined mRNA+protein functional data under ENIGMA v1.2. Details ▾Hide ▴
Evidence considered
- ENIGMA Table 9: variant not listed — no pre-assigned BS3 code
- SuppT3: splicing assay showed no aberration (mRNA-level only
- does not meet BS3 protein requirement)
- SuppT4: no protein functional assay data for this variant
Still missing
- No calibrated protein functional assay data available
Sources
vcep_specifications_table9_v1_2_2024_11_18vcep_supplementarytables_v1_2_2024_11_18
BP1 ENIGMA BP1 Strong requires a missense variant located OUTSIDE a clinically important functional domain AND no splicing predicted (SpliceAI ≤ 0.1). p.Pro2796Ser is located within the BRCA2 DNA binding domain (aa 2481-3186), and SpliceAI delta is 0.16 (> 0.1 threshold). Both conditions fail. Details ▾Hide ▴
Evidence considered
- ENIGMA BP1 requires variant OUTSIDE functional domain + SpliceAI ≤ 0.1
- Pro2796 is inside BRCA2 DNA binding domain (aa 2481-3186)
- SpliceAI max delta: 0.16 (> 0.1)
Sources
BP4 ENIGMA BP4 requires BOTH BayesDel no-AF ≤ 0.18 AND SpliceAI ≤ 0.1 for missense variants inside a clinically important functional domain. Although BayesDel no-AF (-0.202329, ≤ 0.18) is met and the variant lies within the DNA binding domain, SpliceAI max delta is 0.16, which exceeds the 0.1 threshold. BP4 is not met. Details ▾Hide ▴
Evidence considered
- ENIGMA BP4 requires BayesDel ≤ 0.18 AND SpliceAI ≤ 0.1
- BayesDel no-AF: -0.202329 (≤ 0.18 threshold: PASS)
- SpliceAI max delta: 0.16 (> 0.1 threshold: FAIL)
Sources
BP7 ENIGMA BP7 Strong (RNA) for missense variants inside a clinically important functional domain requires BS3 to be met first. BS3 is not met for this variant. BP7 Supporting applies only to silent variants inside functional domains (if BP4 met) or intronic variants outside donor/acceptor positions. NM_000059.4:c.8386C>T is a missense variant and does not meet any BP7 rule condition. The Houdayer et al. 2012 splicing assay showed no splicing aberration, but this mRNA-only data does not independently qualify for BP7 under ENIGMA v1.2 rules for missense variants inside functional domains. Details ▾Hide ▴
Evidence considered
- ENIGMA BP7 Strong (RNA) requires BS3 to be met for missense inside functional domain
- BS3 is not met
- Houdayer 2012: splicing assay showed no aberration (mRNA-level only)
- BP7 Supporting not applicable to missense variants
Sources
cspec ↗vcep_supplementarytables_v1_2_2024_11_18
Not assessed · 4 · no assessment recorded
PS4 No case-control data meeting ENIGMA PS4 thresholds (p ≤ 0.05 and OR ≥ 4) are available for this variant. No case-control studies specific to NM_000059.4:c.8386C>T were identified in the literature. Details ▾Hide ▴
Evidence considered
- ENIGMA PS4 requires case-control study with p ≤ 0.05 and OR ≥ 4
- No case-control data identified in literature or VCEP materials
Still missing
- No case-control data available
Sources
PP1 No co-segregation data are available for quantitative analysis. ENIGMA PP1 requires a likelihood ratio from co-segregation analysis with LR ≥ 2.08:1 (Supporting) or higher. No family segregation studies for NM_000059.4:c.8386C>T were identified. Details ▾Hide ▴
Evidence considered
- ENIGMA PP1 requires quantitative co-segregation analysis with LR ≥ 2.08:1
- No co-segregation data available for this variant
Still missing
- No co-segregation data available
Sources
BS2 ENIGMA BS2 requires proband-level assessment for absence of Fanconi Anemia phenotype features, scored per Specifications Table 8. No proband clinical phenotype data are available for this adjudication. Details ▾Hide ▴
Evidence considered
- ENIGMA BS2 requires proband data scored per Table 8 for absence of FA phenotype
- No proband clinical data available
Still missing
- No proband phenotype data for BS2 assessment
Sources
BS4 ENIGMA BS4 requires a quantitative co-segregation analysis with LR ≤ 0.48:1 toward benign. No family segregation data are available for NM_000059.4:c.8386C>T. Details ▾Hide ▴
Evidence considered
- ENIGMA BS4 requires quantitative co-segregation analysis with LR ≤ 0.48:1
- No co-segregation data available
Still missing
- No co-segregation data available
Sources
Not applicable · 13· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/APVS1 is not applicable for missense variants under ENIGMA BRCA2 v1.2 specifications. PVS1 is reserved for null variants (nonsense, frameshift, canonical ±1,2 splice sites, initiation codon, or exon deletions). NM_000059.4:c.8386C>T is a missense substitution (p.Pro2796Ser). Details ▾Hide ▴
Evidence considered
- ENIGMA BRCA2 v1.2 specification: PVS1 applies only to null variants
- Specifications Table 4: BRCA2 exon 19 PVS1 weight applies to PTC variants only
Sources
cspec ↗vcep_specifications_table4_v1_2_2024_11_18
PS2 VCEPENIGMA BRCA2 v1.2 specification marks PS2 as Not Applicable. Details ▾Hide ▴
PM1 VCEPENIGMA BRCA2 v1.2 specification explicitly marks PM1 as Not Applicable for BRCA2 variants. Domain-level assessment is instead captured through PP3/BP4/BP1 bioinformatic rules based on location within the DNA binding domain (aa 2481-3186). Details ▾Hide ▴
PM3 N/ASkipped per adjudication instructions — trivially not applicable. Details ▾Hide ▴
No further detail was recorded.
PM4 VCEPSkipped per adjudication instructions — trivially not applicable. Details ▾Hide ▴
No further detail was recorded.
PM5 N/AENIGMA BRCA2 v1.2 repurposes PM5 exclusively for protein termination codon (PTC) variants in exons where a proven pathogenic PTC variant has been seen (PM5_PTC). NM_000059.4:c.8386C>T is a missense variant (p.Pro2796Ser), not a PTC/nonsense variant. Classic same-residue missense PM5 is not applicable under this VCEP framework. PM5_N/A is not assigned to exon 19 in Specifications Table 4, but PM5_PTC applies only to truncating variants. Details ▾Hide ▴
Evidence considered
- ENIGMA PM5 is repurposed for PTC variants only (PM5_PTC)
- Specifications Table 4: BRCA2 exon 19 PM5_PTC = Strong (for PTC variants only)
- This is a missense variant
- not eligible for PM5_PTC
Sources
cspec ↗vcep_specifications_table4_v1_2_2024_11_18
PM6 VCEPENIGMA BRCA2 v1.2 specification marks PM6 as Not Applicable. Details ▾Hide ▴
PP2 VCEPENIGMA BRCA2 v1.2 specification marks PP2 as Not Applicable. Details ▾Hide ▴
PP5 VCEPENIGMA BRCA2 v1.2 specification marks PP5 as Not Applicable for BRCA2 variants. Details ▾Hide ▴
BP2 VCEPENIGMA BRCA2 v1.2 specification marks BP2 as Not Applicable. Details ▾Hide ▴
BP3 VCEPSkipped per adjudication instructions — trivially not applicable. Details ▾Hide ▴
No further detail was recorded.
BP6 VCEPENIGMA BRCA2 v1.2 specification marks BP6 as Not Applicable. Details ▾Hide ▴
PS5 N/ASkipped per adjudication instructions — trivially not applicable. Details ▾Hide ▴
No further detail was recorded.
Identifiers
- Gene
- BRCA2
- Transcript
- NM_000059.4
- Coding (HGVS c.)
- NM_000059.4:c.8386C>T
- Protein (HGVS p.)
- NP_000050.3:p.(Pro2796Ser)
- GRCh38
- chr13:32370456 C>T
- GRCh37
- chr13:32944593 C>T
- ClinVar
- 91511
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
28 / 1,613,960 alleles
AF 1.73e-05 · 0 homozygotes · FAF 1.74e-05
gnomAD v2.1
4 / 251,442 alleles
AF 1.59e-05 · 0 homozygotes · FAF 1.12e-05
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 1.7e-05 · 28 / 1,613,960 alleles · 0 hom · FAF 1.7e-05
| African/African American4 / 75,024 | 5.3e-05 |
| European (non-Finnish)24 / 1,179,856 | 2e-05 |
0 alternate alleles recorded in 8 other groups: Remaining individuals, Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish.
gnomAD v2.1
AF 1.6e-05 · 4 / 251,442 alleles · 0 hom · FAF 1.1e-05
| European (non-Finnish)4 / 113,728 | 3.5e-05 |
0 alternate alleles recorded in 7 other groups: African/African American, Admixed American, Ashkenazi Jewish, East Asian, European (Finnish), Remaining individuals, South Asian.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 1.73486e-05; MAF= 0.00173%, 28/1613960 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 5.33163e-05; MAF= 0.00533%, 4/75024 alleles, homozygotes = 0); grpmax FAF= 1.744e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.59082e-05; MAF= 0.00159%, 4/251442 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 3.51716e-05; MAF= 0.00352%, 4/113728 alleles, homozygotes = 0); grpmax FAF= 1.122e-05.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.328
- BayesDel
- -0.202
How the predictions were used
PP3 Although p.Pro2796Ser lies within the BRCA2 DNA binding domain (aa 2481-3186), neither ENIGMA PP3 condition is satisfied: BayesDel no-AF score is -0.202329 (threshold ≥ 0.30 not met) and SpliceAI max delta is 0.16 (threshold ≥ 0.2 not met). No predicted impact on protein function or splicing by ENIGMA bioinformatic thresholds. Details ▾Hide ▴
Evidence considered
- ENIGMA PP3 requires BayesDel no-AF ≥ 0.30 OR SpliceAI ≥ 0.2 for missense inside functional domain
- BayesDel no-AF: -0.202329 (< 0.30 threshold)
- SpliceAI max delta: 0.16 (< 0.2 threshold)
- REVEL: 0.328 (informational only
- ENIGMA does not use REVEL for PP3)
Sources
BP4 ENIGMA BP4 requires BOTH BayesDel no-AF ≤ 0.18 AND SpliceAI ≤ 0.1 for missense variants inside a clinically important functional domain. Although BayesDel no-AF (-0.202329, ≤ 0.18) is met and the variant lies within the DNA binding domain, SpliceAI max delta is 0.16, which exceeds the 0.1 threshold. BP4 is not met. Details ▾Hide ▴
Evidence considered
- ENIGMA BP4 requires BayesDel ≤ 0.18 AND SpliceAI ≤ 0.1
- BayesDel no-AF: -0.202329 (≤ 0.18 threshold: PASS)
- SpliceAI max delta: 0.16 (> 0.1 threshold: FAIL)
Sources
BP7 ENIGMA BP7 Strong (RNA) for missense variants inside a clinically important functional domain requires BS3 to be met first. BS3 is not met for this variant. BP7 Supporting applies only to silent variants inside functional domains (if BP4 met) or intronic variants outside donor/acceptor positions. NM_000059.4:c.8386C>T is a missense variant and does not meet any BP7 rule condition. The Houdayer et al. 2012 splicing assay showed no splicing aberration, but this mRNA-only data does not independently qualify for BP7 under ENIGMA v1.2 rules for missense variants inside functional domains. Details ▾Hide ▴
Evidence considered
- ENIGMA BP7 Strong (RNA) requires BS3 to be met for missense inside functional domain
- BS3 is not met
- Houdayer 2012: splicing assay showed no aberration (mRNA-level only)
- BP7 Supporting not applicable to missense variants
Sources
cspec ↗vcep_supplementarytables_v1_2_2024_11_18
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.16). REVEL score = 0.328. BayesDel score = -0.202329.
9 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata.
Recorded publications
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PMID 22505045 ↗Guidelines for splicing analysis in molecular diagnosis derived from a set of 327 combined in silico/in vitro studies on BRCA1 and BRCA2 variants.Houdayer C et al. · 2012Houdayer et al. 2012 performed a large-scale BRCA1/2 splicing study testing 272 VUSs. NM_000059.4:c.8386C>T (p.Pro2796Ser, legacy 8614C>T) was tested by PAXgene-based transcript analysis and showed no splicing aberration (class C0). The assay used patient-derived RNA and was not allele-specific.Names this variant
Quoted passage
no aberration
Supplementary data (captured in ENIGMA Supplementary Tables 2 and 3); variant not listed in main article text
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PMID 23918944 ↗Tamoxifen and risk of contralateral breast cancer for BRCA1 and BRCA2 mutation carriers.Phillips et al. 2013 analyzed tamoxifen and contralateral breast cancer risk in BRCA1/2 mutation carriers. The paper focuses on known pathogenic mutation carriers and does not report NM_000059.4:c.8386C>T.Does not name this variant
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PMID 24094589 ↗A clinically validated diagnostic second-generation sequencing assay for detection of hereditary BRCA1 and BRCA2 mutations.Bosdet IE et al. · 2013Bosdet et al. 2013 describe a clinically validated NGS assay for BRCA1/2 mutation detection. The paper validates the sequencing methodology and does not report individual variant classifications. NM_000059.4:c.8386C>T is not mentioned.Does not name this variant
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PMID 25741868 ↗Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.Richards et al. 2015 provide the ACMG/AMP standards and guidelines for sequence variant interpretation. This is a methodology framework paper that does not discuss individual variants. NM_000059.4:c.8386C>T is not mentioned.Does not name this variant
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PMID 30254663 ↗Dealing With BRCA1/2 Unclassified Variants in a Cancer Genetics Clinic: Does Cosegregation Analysis Help?Zuntini R et al. · 2018Zuntini et al. 2018 investigated cosegregation analysis for BRCA1/2 unclassified variants in a cancer genetics clinic. The paper discusses general approaches to VUS classification using cosegregation but does not specifically study NM_000059.4:c.8386C>T.Does not name this variant
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PMID 30263092 ↗Rapid detection of copy number variations and point mutations in BRCA1/2 genes using a single workflow by ion semiconductor sequencing pipeline.Germani A et al. · 2018Germani et al. 2018 describe a rapid NGS pipeline for BRCA1/2 mutation detection including CNVs and point mutations. The paper is a methods/validation study and does not report individual variant assessments. NM_000059.4:c.8386C>T is not mentioned.Does not name this variant
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PMID 17392385 ↗American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography.Saslow D et al. · 2007Saslow et al. 2007 present American Cancer Society guidelines for breast MRI screening. The paper does not discuss individual genetic variants. NM_000059.4:c.8386C>T is not mentioned.Does not name this variant
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PMID 20301425 ↗BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer.Adam MP et al. · 1993GeneReviews entry for BRCA1/2-associated hereditary breast and ovarian cancer. Provides clinical characteristics and management guidelines but does not assess individual variants. NM_000059.4:c.8386C>T is not discussed.Does not name this variant
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PMID 28492532 ↗Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.No paper-specific finding is recorded.
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
28 / 1,613,960 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.160
Open source ↗
ClinVar
7 Uncertain significance · 4 Likely benign · 1 Benign
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
- ClinGen CSpec ↗cspec.genome.network/cspec/ui/svi/doc/1535438831
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/91511/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/13-32944593-C-T?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr13-32370456-C-T?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/13-32370456-C-T
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000059.4%3Ac.8386…
- OncoKB ↗www.oncokb.org/gene/BRCA2/P2796S
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=BRCA2+c.8386C%3ET
- Cancer hotspots ↗www.cancerhotspots.org/
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= 1.73486e-05; MAF= 0.00173%, 28/1613960 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 5.33163e-05; MAF= 0.00533%, 4/75024 alleles, homozygotes = 0); grpmax FAF= 1.744e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.59082e-05; MAF= 0.00159%, 4/251442 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 3.51716e-05; MAF= 0.00352%, 4/113728 alleles, homozygotes = 0); grpmax FAF= 1.122e-05.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Uncertain significance (7 clinical laboratories) and as Likely benign (4 clinical laboratories) and as Benign (1 clinical laboratory). (ClinVarID = 91511)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.16). REVEL score = 0.328. BayesDel score = -0.202329.
Functional
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. BRCA2, a tumor suppressor involved in the DNA damage response, is mutated in various cancer types.
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.