About BRCA2
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
BRCA2 c.4516T>C, p.(Phe1506Leu)
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 v1.2.0. 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 missense variant lies outside the BRCA2 clinically important domains defined by the ENIGMA BRCA2 framework (PALB2-binding domain amino acids 10-40 and DNA-binding domain amino acids 2481-3186), and SpliceAI predicts no significant splice effect (max delta score 0.00). This meets BRCA2 BP1_Strong.
Recorded classification: Uncertain significance
Official ENIGMA BRCA1/BRCA2 v1.2 Table 3 final-classification framework was used. Applied evidence comprises BP1_Strong as a single strong benign criterion, with no applied pathogenic criteria. A single strong benign criterion alone does not meet ENIGMA Table 3 thresholds for Likely Benign or Benign classification, and no pathogenic classification threshold is met.
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
3 / 1,613,958 alleles
gnomAD v4.1: 3 / 1,613,958 alleles. Recorded AF 1.85878e-06. Recorded homozygote count 0.
gnomAD v2.1
Absent from gnomAD v2.1.
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 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
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
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 · 4 not met · 13 not assessed · 10 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
The BRCA2 c.4516T>C (p.Phe1506Leu; p.F1506L) variant has been reported in ClinVar with conflicting classifications, including uncertain significance and likely benign submissions.
This variant is absent from gnomAD v2.1 and present at very low frequency in gnomAD v4.1 (3/1,613,958 alleles; AF 0.00019%), with the highest observed frequency 1/6,062 alleles in the Middle Eastern population (AF 0.01650%).
No variant-specific calibrated functional assay classification was identified in the reviewed BRCA2 ENIGMA functional tables, and no variant-specific reviewed functional evidence was identified in curated somatic reviewer resources.
The substitution lies outside the BRCA2 clinically important domains defined by ENIGMA, SpliceAI predicts no significant splice effect (max delta score 0.00), and missense predictor scores are low (REVEL 0.093; BayesDel no-AF -0.650576), supporting a benign computational profile.
No criteria match.
Met · 1
BP1 StrongThis missense variant lies outside the BRCA2 clinically important domains defined by the ENIGMA BRCA2 framework (PALB2-binding domain amino acids 10-40 and DNA-binding domain amino acids 2481-3186), and SpliceAI predicts no significant splice effect (max delta score 0.00). This meets BRCA2 BP1_Strong. Details ▾Hide ▴
Rule
ENIGMA BRCA2 BP1_Strong: missense variant outside clinically important domains and SpliceAI ≤0.1.
Evidence considered
- Protein change p.(Phe1506Leu) is outside aa 10-40 and aa 2481-3186.
- SpliceAI max delta score 0.00.
Sources
Not met · 4 · evaluated, threshold not reached
PVS1 This variant is a missense substitution, not a nonsense, frameshift, canonical ±1/2 splice, or other predicted loss-of-function variant, and SpliceAI predicts no significant splice effect (max delta score 0.00). Available evidence does not support applying PVS1 or PVS1(RNA). Details ▾Hide ▴
Rule
ENIGMA BRCA2 PVS1 requires a qualifying null variant or qualifying RNA evidence.
Evidence considered
- BRCA2 loss of function is an established disease mechanism in the ENIGMA BRCA2 framework.
- NM_000059.4:c.4516T>C encodes p.(Phe1506Leu) / p.(F1506L).
- SpliceAI max delta score 0.00.
Still missing
- No variant-specific RNA study demonstrating an abnormal transcript effect was identified.
Sources
PM2 This variant is absent from gnomAD v2.1 but is present in gnomAD v4.1 at 3/1,613,958 alleles (AF 0.00019%), with the highest observed frequency 1/6,062 alleles in the Middle Eastern population (AF 0.01650%). ENIGMA BRCA2 applies PM2 only for variants absent from control datasets, so PM2 was not applied. Details ▾Hide ▴
Rule
ENIGMA BRCA2 PM2_Supporting requires absence from controls.
Evidence considered
- gnomAD v2.1 absent.
- gnomAD v4.1 total AF 1.8587844293345923e-06 (3/1613958).
- Highest observed population frequency 0.0001649620587264929 (1/6062) in Middle Eastern individuals.
Still missing
- The ENIGMA rule refers to absence in gnomAD v2.1 and v3.1 with adequate depth
- no v3.1-specific record was retrieved here.
Sources
PP3 This missense variant lies outside the BRCA2 clinically important domains used by the ENIGMA BRCA2 framework, and SpliceAI predicts no significant splice effect (max delta score 0.00). Missense predictor scores are low, with REVEL 0.093 and BayesDel no-AF -0.650576, which are not consistent with the ENIGMA PP3 thresholds for pathogenic computational evidence, so PP3 was not applied. Details ▾Hide ▴
Rule
ENIGMA BRCA2 PP3 applies to qualifying domain missense variants with BayesDel no-AF ≥0.30 or to variants with SpliceAI ≥0.2.
Evidence considered
- Clinically important BRCA2 domains for PP3 are aa 10-40 and aa 2481-3186.
- Protein change is p.(Phe1506Leu)
- outside those domains.
- SpliceAI max delta score 0.00.
- REVEL 0.093.
- BayesDel no-AF -0.650576.
Sources
BP4 SpliceAI predicts no significant splice effect (max delta score 0.00), REVEL is low at 0.093, and BayesDel no-AF is -0.650576, consistent with a benign computational profile. However, ENIGMA BRCA2 applies BP4 for missense variants only when they are inside a clinically important domain, and p.(Phe1506Leu) lies outside those domains, so BP4 was not applied. Details ▾Hide ▴
Rule
ENIGMA BRCA2 BP4 requires a qualifying domain-context missense or other specified variant class with benign computational evidence.
Evidence considered
- Protein change p.(Phe1506Leu) is outside aa 10-40 and aa 2481-3186.
- SpliceAI max delta score 0.00.
- REVEL 0.093.
- BayesDel no-AF -0.650576.
Sources
Not assessed · 13 · no assessment recorded
PS1 No qualifying previously classified pathogenic or likely pathogenic variant causing the same amino acid change or the same predicted splice effect was identified from the available evidence, so PS1 was not applied. Details ▾Hide ▴
Rule
ENIGMA BRCA2 PS1 requires a previously classified pathogenic/likely pathogenic reference variant with the same amino acid change or same predicted splice effect.
Evidence considered
- ClinVar contains submissions for this variant but no qualifying PS1 reference variant was established from the reviewed materials.
Still missing
- A dedicated codon-level review of previously classified BRCA2 variants at this site could further confirm whether any PS1 reference variant exists.
Sources
PS3 No variant-specific calibrated functional study assignment supporting a damaging effect was identified for this variant, so PS3 was not applied. Details ▾Hide ▴
Rule
ENIGMA BRCA2 PS3 requires variant-specific well-established functional evidence supportive of a damaging effect.
Evidence considered
- No exact match for c.4516T>C / p.(Phe1506Leu) was identified in the ENIGMA BRCA functional table.
- OncoKB did not identify variant-specific reviewed functional evidence.
Still missing
- No reviewed functional study showing a damaging effect for p.(Phe1506Leu) was identified.
Sources
PS4 No case-control study, odds ratio, or other qualifying evidence showing increased prevalence in affected individuals was identified for this variant, so PS4 was not applied. Details ▾Hide ▴
Rule
ENIGMA BRCA2 PS4 requires significantly increased prevalence in affected individuals compared with controls.
Evidence considered
- ClinVar reports conflicting submissions but not a qualifying PS4 case-control result.
- No exact variant match was identified in the reviewed ENIGMA posterior-probability and multifactorial tables.
Still missing
- No qualifying case-control or prevalence data for this exact variant were identified.
Sources
PM3 No evidence was identified that this variant was observed in trans with another BRCA2 pathogenic variant in an individual with a BRCA2-related Fanconi anemia phenotype, so PM3 was not applied. Details ▾Hide ▴
Rule
ENIGMA BRCA2 PM3 is restricted to BRCA2-related Fanconi anemia evidence with point-based scoring.
Evidence considered
- No qualifying PM3 evidence was found in the reviewed materials.
Still missing
- No phase-confirmed Fanconi anemia case data were identified.
Sources
PP1 No quantitative co-segregation evidence was identified for this variant, so PP1 was not applied. Details ▾Hide ▴
Rule
ENIGMA BRCA2 PP1 requires a quantitative segregation likelihood ratio of at least 2.08:1.
Evidence considered
- No qualifying segregation data were found in the reviewed materials.
Still missing
- No segregation likelihood ratio or family-based segregation analysis was identified.
Sources
PP4 No exact-variant multifactorial clinical likelihood ratio meeting the ENIGMA PP4 threshold was identified, so PP4 was not applied. Details ▾Hide ▴
Rule
ENIGMA BRCA2 PP4 requires a multifactorial likelihood ratio toward pathogenicity.
Evidence considered
- ENIGMA PP4 requires a multifactorial likelihood ratio ≥2.08.
- No exact clinical-history LR entry for c.4516T>C was identified in the BRCA2 LR workbook.
Still missing
- The BRCA2 clinical-history likelihood-ratio workbook did not yield an exact row for c.4516T>C.
- No other exact-variant combined multifactorial likelihood ratio was identified.
Sources
cspec ↗PMID:31853058 ↗vcep_pmid_31853058_brca2_clinical_history_lrvcep_pmid_17924331_easton_2007_ajhgPMID:17924331 ↗
BA1 This variant is present in gnomAD v4.1, but the ENIGMA BRCA2 BA1 rule is based on filter allele frequency from specified gnomAD datasets, and no qualifying BA1-level filter allele frequency was retrieved. BA1 was not applied. Details ▾Hide ▴
Rule
ENIGMA BRCA2 BA1 requires filter allele frequency >0.1% in the specified gnomAD framework.
Evidence considered
- gnomAD v4.1 total AF 0.00019%.
- Highest observed population AF 0.01650% in Middle Eastern individuals.
Still missing
- No qualifying filter allele frequency above the BA1 threshold was retrieved from the required ENIGMA datasets.
Sources
BS1 This variant is present in gnomAD v4.1, including 1/6,062 alleles in the Middle Eastern population (AF 0.01650%), but the ENIGMA BRCA2 BS1 rule is based on filter allele frequency from specified gnomAD datasets, and no qualifying BS1 filter allele frequency was retrieved. BS1 was not applied. Details ▾Hide ▴
Rule
ENIGMA BRCA2 BS1 uses filter allele frequency thresholds >0.002% and >0.01% in the specified gnomAD framework.
Evidence considered
- Highest observed population AF 0.01650% (1/6062).
- No qualifying filter allele frequency value was retrieved.
Still missing
- No qualifying filter allele frequency from the required ENIGMA datasets was retrieved.
Sources
BS2 No point-based evidence from unaffected or non-Fanconi anemia observations was identified for this variant, so BS2 was not applied. Details ▾Hide ▴
Rule
ENIGMA BRCA2 BS2 requires point-based evidence in the absence of Fanconi anemia features.
Evidence considered
- No BS2 scoring evidence was found in the reviewed materials.
Still missing
- No qualifying BS2 proband-level observations were identified.
Sources
BS3 No variant-specific calibrated functional study assignment showing no damaging effect was identified for this variant, so BS3 was not applied. Details ▾Hide ▴
Rule
ENIGMA BRCA2 BS3 requires variant-specific well-established functional evidence showing no damaging effect.
Evidence considered
- No exact match for c.4516T>C / p.(Phe1506Leu) was identified in the ENIGMA BRCA functional table.
- OncoKB did not identify variant-specific reviewed functional evidence.
Still missing
- No reviewed functional study showing normal BRCA2 function for p.(Phe1506Leu) was identified.
Sources
BS4 No quantitative non-segregation evidence or segregation likelihood ratio against pathogenicity was identified for this variant, so BS4 was not applied. Details ▾Hide ▴
Rule
ENIGMA BRCA2 BS4 requires a quantitative segregation likelihood ratio of 0.48:1 or lower against pathogenicity.
Evidence considered
- No exact variant non-segregation evidence was identified in the reviewed materials.
Still missing
- No qualifying family-based non-segregation analysis was identified.
Sources
BP5 No exact-variant multifactorial clinical likelihood ratio meeting the ENIGMA BP5 threshold was identified, so BP5 was not applied. Details ▾Hide ▴
Rule
ENIGMA BRCA2 BP5 requires a multifactorial likelihood ratio against pathogenicity.
Evidence considered
- ENIGMA BP5 requires a multifactorial likelihood ratio ≤0.48.
- No exact clinical-history LR entry for c.4516T>C was identified in the BRCA2 LR workbook.
Still missing
- The BRCA2 clinical-history likelihood-ratio workbook did not yield an exact row for c.4516T>C.
- No other exact-variant combined multifactorial likelihood ratio against pathogenicity was identified.
Sources
cspec ↗PMID:31853058 ↗vcep_pmid_31853058_brca2_clinical_history_lrvcep_pmid_17924331_easton_2007_ajhgPMID:17924331 ↗
BP7 No variant-specific RNA study showing a normal transcript outcome was identified for this missense variant, so BP7 was not applied. Details ▾Hide ▴
Rule
ENIGMA BRCA2 BP7 requires qualifying RNA or specified silent/intronic evidence conditions.
Evidence considered
- SpliceAI max delta score 0.00.
- No RNA study establishing a normal transcript outcome was identified.
Still missing
- No reviewed RNA assay for c.4516T>C demonstrating no abnormal splicing was identified.
Sources
Not applicable · 10· recorded as not applicable Show reasons ▾Hide reasons ▴
PS2 N/APS2 is not used in this BRCA2 VCEP framework. Details ▾Hide ▴
Rule
Not applicable in ENIGMA BRCA2 v1.2.
Evidence considered
- ENIGMA BRCA2 marks PS2 as not applicable.
Sources
PM1 N/APM1 is not used as a standalone criterion in this BRCA2 VCEP framework because domain context is incorporated into other criteria. Details ▾Hide ▴
Rule
Not applicable in ENIGMA BRCA2 v1.2.
Evidence considered
- ENIGMA BRCA2 marks PM1 as not applicable.
Sources
PM4 N/APM4 is not used in this BRCA2 VCEP framework. Details ▾Hide ▴
Rule
Not applicable in ENIGMA BRCA2 v1.2.
Evidence considered
- ENIGMA BRCA2 marks PM4 as not applicable.
Sources
PM5 N/AIn this BRCA2 VCEP framework, PM5 is restricted to protein-truncating variants under the PM5_PTC rules. This variant is a missense substitution, so PM5 is not applicable. Details ▾Hide ▴
Rule
ENIGMA BRCA2 PM5_PTC only.
Evidence considered
- NM_000059.4:c.4516T>C is a missense variant p.(Phe1506Leu).
- ENIGMA BRCA2 PM5 is limited to genomic PTC changes.
Sources
cspec ↗vcep_specifications_table4_v1_2_2024_11_18
PM6 N/APM6 is not used in this BRCA2 VCEP framework. Details ▾Hide ▴
Rule
Not applicable in ENIGMA BRCA2 v1.2.
Evidence considered
- ENIGMA BRCA2 marks PM6 as not applicable.
Sources
PP2 N/APP2 is not used in this BRCA2 VCEP framework. Details ▾Hide ▴
Rule
Not applicable in ENIGMA BRCA2 v1.2.
Evidence considered
- ENIGMA BRCA2 marks PP2 as not applicable.
Sources
PP5 N/APP5 is not for use in this VCEP framework. Details ▾Hide ▴
Rule
Not applicable in ENIGMA BRCA2 v1.2.
Evidence considered
- ENIGMA BRCA2 marks PP5 as not applicable.
Sources
BP2 N/ABP2 is not used in this BRCA2 VCEP framework. Details ▾Hide ▴
Rule
Not applicable in ENIGMA BRCA2 v1.2.
Evidence considered
- ENIGMA BRCA2 marks BP2 as not applicable.
Sources
BP3 N/ABP3 is not used in this BRCA2 VCEP framework. Details ▾Hide ▴
Rule
Not applicable in ENIGMA BRCA2 v1.2.
Evidence considered
- ENIGMA BRCA2 marks BP3 as not applicable.
Sources
BP6 N/ABP6 is not used in this BRCA2 VCEP framework. Details ▾Hide ▴
Rule
Not applicable in ENIGMA BRCA2 v1.2.
Evidence considered
- ENIGMA BRCA2 marks BP6 as not applicable.
Sources
Identifiers
- Gene
- BRCA2
- Transcript
- NM_000059.4
- Coding (HGVS c.)
- NM_000059.4:c.4516T>C
- Protein (HGVS p.)
- NP_000050.3:p.(Phe1506Leu)
- GRCh38
- chr13:32338871 T>C
- GRCh37
- chr13:32913008 T>C
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
3 / 1,613,958 alleles
AF 1.86e-06 · 0 homozygotes
gnomAD v2.1
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 1.9e-06 · 3 / 1,613,958 alleles · 0 hom
| Middle Eastern1 / 6,062 | 0.00016 |
| African/African American1 / 75,040 | 1.3e-05 |
| European (non-Finnish)1 / 1,179,938 | 8.5e-07 |
0 alternate alleles recorded in 7 other groups: Remaining individuals, Admixed American, European (Finnish), Amish, East Asian, South Asian, Ashkenazi Jewish.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 1.85878e-06; MAF= 0.00019%, 3/1613958 alleles, homozygotes = 0) and has highest observed frequency in the Middle Eastern population (AF= 0.000164962; MAF= 0.01650%, 1/6062 alleles, homozygotes = 0).
gnomAD v2.1
Absent from gnomAD v2.1.
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
PP3 This missense variant lies outside the BRCA2 clinically important domains used by the ENIGMA BRCA2 framework, and SpliceAI predicts no significant splice effect (max delta score 0.00). Missense predictor scores are low, with REVEL 0.093 and BayesDel no-AF -0.650576, which are not consistent with the ENIGMA PP3 thresholds for pathogenic computational evidence, so PP3 was not applied. Details ▾Hide ▴
Rule
ENIGMA BRCA2 PP3 applies to qualifying domain missense variants with BayesDel no-AF ≥0.30 or to variants with SpliceAI ≥0.2.
Evidence considered
- Clinically important BRCA2 domains for PP3 are aa 10-40 and aa 2481-3186.
- Protein change is p.(Phe1506Leu)
- outside those domains.
- SpliceAI max delta score 0.00.
- REVEL 0.093.
- BayesDel no-AF -0.650576.
Sources
BP4 SpliceAI predicts no significant splice effect (max delta score 0.00), REVEL is low at 0.093, and BayesDel no-AF is -0.650576, consistent with a benign computational profile. However, ENIGMA BRCA2 applies BP4 for missense variants only when they are inside a clinically important domain, and p.(Phe1506Leu) lies outside those domains, so BP4 was not applied. Details ▾Hide ▴
Rule
ENIGMA BRCA2 BP4 requires a qualifying domain-context missense or other specified variant class with benign computational evidence.
Evidence considered
- Protein change p.(Phe1506Leu) is outside aa 10-40 and aa 2481-3186.
- SpliceAI max delta score 0.00.
- REVEL 0.093.
- BayesDel no-AF -0.650576.
Sources
BP7 No variant-specific RNA study showing a normal transcript outcome was identified for this missense variant, so BP7 was not applied. Details ▾Hide ▴
Rule
ENIGMA BRCA2 BP7 requires qualifying RNA or specified silent/intronic evidence conditions.
Evidence considered
- SpliceAI max delta score 0.00.
- No RNA study establishing a normal transcript outcome was identified.
Still missing
- No reviewed RNA assay for c.4516T>C demonstrating no abnormal splicing was identified.
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.093. BayesDel score = -0.650576.
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
3 / 1,613,958 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
- ClinGen CSpec ↗cspec.genome.network/cspec/ui/svi/doc/1535438831
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/231190/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/13-32913008-T-C?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr13-32338871-T-C?dataset=gn…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000059.4%3Ac.4516…
- OncoKB ↗www.oncokb.org/gene/BRCA2/F1506L
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=BRCA2+c.4516T%3EC
- 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= 1.85878e-06; MAF= 0.00019%, 3/1613958 alleles, homozygotes = 0) and has highest observed frequency in the Middle Eastern population (AF= 0.000164962; MAF= 0.01650%, 1/6062 alleles, homozygotes = 0).
gnomAD v2.1
Absent from gnomAD v2.1.
ClinVar
This variant has been reported in ClinVar as Uncertain significance (3 clinical laboratories) and as Likely benign (2 clinical laboratories) and as Uncertain Significance (1 clinical laboratory).
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.093. BayesDel score = -0.650576.
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.