About BRCA2
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
BRCA2 c.8149G>T, p.(Ala2717Ser)
Classification
Benign
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is benign. Select a step to read what it means.
Benign.A 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: 3
Pathogenic criteria applied · 0
No pathogenic criterion marked as applied in the recorded assessment.
Benign criteria applied · 3
BA1Stand alone
BA1 · stand alone
This variant exceeds the BRCA2 ENIGMA BA1 population threshold. The grpmax filtering allele frequency is 0.00162114 in gnomAD v2.1 and 0.00163682 in gnomAD v4.1, both above the BA1 threshold of 0.001 in non-founder populations.
BS3Strong
BS3 · strong
In the BRCA2 ENIGMA curated functional dataset, this variant was assigned BS3 Strong. Published calibrated functional studies showed protein function similar to benign control variants, and RNA data in the same curation entry showed no aberrant splicing.
BP6Supporting
BP6 · supporting
Expert panel ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel, ClinGen classified as Benign.
Recorded classification: Benign
ENIGMA BRCA1/BRCA2 Specification v1.2 Table 3 final-classification framework (official ClinGen CSPEC/VCEP criteria-combination rules).
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
2,248 / 1,614,110 alleles
gnomAD v4.1: 2,248 / 1,614,110 alleles. Recorded AF 0.00139272. Recorded homozygote count 2.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.00111433; MAF= 0.11143%, 315/282680 alleles, homozygotes = 0) and has highest observed frequency in the Remaining individuals population (AF= 0.00207814; MAF= 0.20781%, 15/7218 alleles, homozygotes = 0); grpmax FAF= 0.00162114.
SpliceAI score
0.030 maximum delta
Recorded SpliceAI maximum delta score: 0.030. Refer to the recorded PP3/BP4 rationale for interpretation.
No listed criterion applied
SpliceAI ↗
ClinVar submissions
36 reported laboratory submissions
22 Benign · 11 Likely benign · 2 Uncertain significance · 1 Likely Benign.
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.
COSMIC
Cancer Hotspots
Somatic evidence
3 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV66460731, n = 3 times).
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: 3 met · 7 not met · 8 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.8149G>T (p.Ala2717Ser) variant has been reported in ClinVar as Benign with expert panel review, and curated cancer resources did not identify it as a statistically significant hotspot while OncoKB describes it as likely neutral.
This variant is present in population databases at a frequency above the BRCA2 ENIGMA BA1 threshold, with grpmax filtering allele frequency 0.00162114 in gnomAD v2.1 and 0.00163682 in gnomAD v4.1, supporting a benign population interpretation.
In curated BRCA2 functional studies, this variant showed protein function similar to benign control variants, and associated RNA data showed no aberrant splicing, supporting BS3_Strong.
Computational evidence does not support a damaging interpretation under the BRCA2 ENIGMA rules: the BayesDel no-AF score is -0.0816274, REVEL is 0.535, and no SpliceAI score demonstrating splice impact was identified, so PP3 is not met and BP4 could not be fully applied.
No criteria match.
Met · 3
BA1 Stand aloneThis variant exceeds the BRCA2 ENIGMA BA1 population threshold. The grpmax filtering allele frequency is 0.00162114 in gnomAD v2.1 and 0.00163682 in gnomAD v4.1, both above the BA1 threshold of 0.001 in non-founder populations. Details ▾Hide ▴
Rule
BA1 applies when FAF >0.001 in a non-founder population.
Evidence considered
- gnomAD v2.1 grpmax FAF 0.00162114
- gnomAD v4.1 grpmax FAF 0.00163682
- ENIGMA BA1 threshold FAF >0.001
Sources
BS3 StrongIn the BRCA2 ENIGMA curated functional dataset, this variant was assigned BS3 Strong. Published calibrated functional studies showed protein function similar to benign control variants, and RNA data in the same curation entry showed no aberrant splicing. Details ▾Hide ▴
Rule
BS3 applies when well-established functional studies show no damaging effect on protein function.
Evidence considered
- ENIGMA Table 9 exact variant row: BS3 Strong for c.8149G>T p.(Ala2717Ser)
Sources
vcep_specifications_table9_v1_2_2024_11_18cspec ↗
BP6 SupportingExpert panel ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel, ClinGen classified as Benign. Details ▾Hide ▴
Not met · 7 · evaluated, threshold not reached
PS1 No evidence was identified that this variant produces the same amino-acid change or the same predicted splice effect as a previously classified pathogenic or likely pathogenic BRCA2 variant. PS1 is not met based on the available data. Details ▾Hide ▴
Rule
PS1 requires the same amino-acid change as a previously classified pathogenic variant, or the same splice effect as a previously classified pathogenic/likely pathogenic variant.
Evidence considered
- BRCA2 ENIGMA PS1 rule review
- ClinVar exact variant context
Still missing
- A dedicated same-amino-acid or same-splice comparator review was not identified in the available materials.
Sources
PS3 Published functional data curated by the BRCA2 ENIGMA expert framework showed protein function similar to benign control variants rather than a damaging effect, so PS3 is not met. Details ▾Hide ▴
Rule
PS3 requires well-established functional studies showing a damaging effect.
Evidence considered
- ENIGMA Table 9 exact variant entry c.8149G>T p.(Ala2717Ser) assigned BS3 Strong
Sources
vcep_specifications_table9_v1_2_2024_11_18cspec ↗
PS4 No case-control evidence was identified showing that this variant is significantly enriched in affected individuals, and the variant is also observed at a population frequency that is too high to support PS4. Available evidence does not support increased prevalence in affected individuals. Details ▾Hide ▴
Rule
PS4 requires significant enrichment in affected individuals versus controls.
Evidence considered
- ENIGMA PS4 rule
- gnomAD population frequency
- ENIGMA ST7 reference-set row for c.8149G>T
Still missing
- No formal exact-variant case-control analysis with odds ratio and confidence interval was identified.
Sources
PM2 This variant is not absent from population databases. In gnomAD v2.1 the overall allele frequency is 0.11143% with grpmax FAF 0.00162114, and in gnomAD v4.1 the overall allele frequency is 0.13927% with grpmax FAF 0.00163682, so the ENIGMA PM2 absence criterion is not met. Details ▾Hide ▴
Rule
PM2_Supporting requires absence from controls in sufficiently covered gnomAD data.
Evidence considered
- gnomAD v2.1 frequency data
- gnomAD v4.1 frequency data
- ENIGMA PM2 threshold
Sources
PP3 This missense variant lies in the BRCA2 DNA-binding region, but the available computational evidence does not meet the ENIGMA PP3 threshold. The BayesDel no-AF score is -0.0816274, which is below the required threshold of 0.30, and no SpliceAI result showing a score of at least 0.2 was identified. Details ▾Hide ▴
Rule
For BRCA2, PP3 requires BayesDel no-AF >=0.30 for qualifying missense variants in a clinically important domain and/or SpliceAI >=0.2 for predicted splice impact.
Evidence considered
- BayesDel no-AF score -0.0816274
- REVEL score 0.535
- ENIGMA PP3 thresholds
Still missing
- No SpliceAI score was available in the reviewed data.
Sources
BP1 This missense variant is located at codon 2717 within the BRCA2 DNA-binding region defined by ENIGMA as a clinically important functional domain (amino acids 2481-3186). BP1, which is reserved for variants outside these domains without predicted splice impact, is not met. Details ▾Hide ▴
Rule
BP1_Strong applies to qualifying missense or silent variants outside clinically important domains with no predicted splice impact.
Evidence considered
- ENIGMA domain definition for BRCA2 DNA binding region aa 2481-3186
Sources
BP4 The BayesDel no-AF score is -0.0816274, which is consistent with the benign side of the BRCA2 ENIGMA threshold, but BP4 for a missense variant in a clinically important domain also requires SpliceAI less than or equal to 0.1. Because no SpliceAI result was identified, BP4 is not met from the available data. Details ▾Hide ▴
Rule
For qualifying BRCA2 missense variants in a clinically important domain, BP4 requires BayesDel no-AF <=0.18 and SpliceAI <=0.1.
Evidence considered
- BayesDel no-AF score -0.0816274
- ENIGMA BP4 rule requires BayesDel <=0.18 and SpliceAI <=0.1
Still missing
- No SpliceAI score was available in the reviewed data.
Sources
Not assessed · 8 · no assessment recorded
PM3 No evidence was identified showing this variant in trans with another BRCA2 variant in a patient with a phenotype consistent with BRCA2-related Fanconi anemia. PM3 was not assessed from the available data. Details ▾Hide ▴
Rule
PM3 requires in-trans observations in BRCA2-related Fanconi anemia under the ENIGMA point-based framework.
Evidence considered
- BRCA2 ENIGMA PM3 rule
Still missing
- No Fanconi-anemia-specific genotype/phenotype evidence was identified.
Sources
PP1 No quantitative co-segregation evidence was identified for this variant in affected relatives. PP1 was not assessed from the available data. Details ▾Hide ▴
Rule
PP1 requires quantitative co-segregation evidence meeting ENIGMA likelihood-ratio thresholds.
Evidence considered
- BRCA2 ENIGMA PP1 rule
- ClinVar exact variant context
Still missing
- No segregation likelihood ratio or informative family study was identified.
Sources
PP4 No variant-specific clinical-history likelihood ratio meeting ENIGMA thresholds was identified for this variant, so PP4 was not assessed. Details ▾Hide ▴
Rule
PP4 in this framework requires a clinical-history likelihood ratio >=2.08.
Evidence considered
- ENIGMA PP4 clinical-history LR framework
- Li 2020 BRCA2 LR workbook exact-variant lookup
Still missing
- The Li 2020 BRCA2 clinical-history LR workbook did not identify an exact variant row for c.8149G>T.
Sources
BS1 Population frequency evidence was captured under BA1. Although the variant also exceeds the BS1 thresholds, BS1 was not separately applied to avoid double-counting the same population data. Details ▾Hide ▴
Rule
Do not double-count BS1 when BA1 already captures the population evidence.
Evidence considered
- Same population evidence used for BA1
Sources
BS2 No evidence was identified showing this variant in individuals without features of BRCA2-related Fanconi anemia under the ENIGMA point-based BS2 framework. BS2 was not assessed. Details ▾Hide ▴
Rule
BS2 requires ENIGMA point-based evidence in individuals lacking Fanconi-anemia features.
Evidence considered
- BRCA2 ENIGMA BS2 rule
Still missing
- No BS2 point-based proband data were identified.
Sources
BS4 No quantitative lack-of-segregation evidence was identified for this variant in affected relatives. BS4 was not assessed from the available data. Details ▾Hide ▴
Rule
BS4 requires quantitative lack-of-segregation evidence meeting ENIGMA likelihood-ratio thresholds.
Evidence considered
- BRCA2 ENIGMA BS4 rule
- reference-set review did not provide a directly usable BS4 likelihood ratio
Still missing
- No segregation likelihood ratio in the benign direction was identified.
Sources
BP5 No variant-specific clinical-history likelihood ratio in the benign direction was identified for this variant, so BP5 was not assessed. Details ▾Hide ▴
Rule
BP5 in this framework requires a clinical-history likelihood ratio <=0.48.
Evidence considered
- ENIGMA BP5 clinical-history LR framework
- Li 2020 BRCA2 LR workbook exact-variant lookup
Still missing
- The Li 2020 BRCA2 clinical-history LR workbook did not identify an exact variant row for c.8149G>T.
Sources
BP7 RNA evidence curated for this variant reported no aberrant splicing, but the available materials did not provide a direct ENIGMA BP7 assignment for this missense variant. BP7 was therefore not separately assessed. Details ▾Hide ▴
Rule
BP7 is applied under specific ENIGMA RNA-only conditions and was not directly assigned here.
Evidence considered
- ENIGMA Table 9 notes no aberrant splicing for c.8149G>T
Still missing
- No direct BP7 code assignment was identified for this exact variant.
Sources
Not applicable · 10· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/AThis is a missense substitution, not a nonsense, frameshift, or canonical +/-1,2 splice-site variant, and no RNA evidence was identified showing a null transcript effect. Under the BRCA2 ENIGMA framework, PVS1 is therefore not applicable. Details ▾Hide ▴
Rule
BRCA2 ENIGMA PVS1 applies to null variants or qualifying RNA evidence, not to an ordinary missense variant without demonstrated null effect.
Evidence considered
- BRCA2 ENIGMA PVS1 rules
- generic PVS1 scaffold confirms this variant is outside default null-variant buckets
Sources
PS2 VCEPThe BRCA2 ENIGMA specification marks PS2 as not applicable in this framework. Details ▾Hide ▴
VCEP rule
Criterion not used by this VCEP framework.
Evidence considered
- BRCA2 ENIGMA criterion applicability table
Sources
PM1 VCEPThe BRCA2 ENIGMA specification marks PM1 as not applicable in this framework. Details ▾Hide ▴
VCEP rule
Criterion not used by this VCEP framework.
Evidence considered
- BRCA2 ENIGMA criterion applicability table
Sources
PM4 VCEPThe BRCA2 ENIGMA specification marks PM4 as not applicable in this framework. Details ▾Hide ▴
VCEP rule
Criterion not used by this VCEP framework.
Evidence considered
- BRCA2 ENIGMA criterion applicability table
Sources
PM5 N/AFor BRCA2 in this ENIGMA framework, PM5 is repurposed for protein-truncating variants rather than classic same-residue missense logic. Because this variant is a missense substitution, PM5 is not applicable. Details ▾Hide ▴
Rule
BRCA2 ENIGMA PM5 applies to qualifying truncating variants, not to this missense variant.
Evidence considered
- PM5 candidates artifact states BRCA2 PM5 mode is PTC-specific
Sources
cspec ↗pm5_candidates
PM6 VCEPThe BRCA2 ENIGMA specification marks PM6 as not applicable in this framework. Details ▾Hide ▴
VCEP rule
Criterion not used by this VCEP framework.
Evidence considered
- BRCA2 ENIGMA criterion applicability table
Sources
PP2 VCEPThe BRCA2 ENIGMA specification marks PP2 as not applicable in this framework. Details ▾Hide ▴
VCEP rule
Criterion not used by this VCEP framework.
Evidence considered
- BRCA2 ENIGMA criterion applicability table
Sources
PP5 VCEPThe BRCA2 ENIGMA specification marks PP5 as not applicable in this framework. Details ▾Hide ▴
VCEP rule
Criterion not used by this VCEP framework.
Evidence considered
- BRCA2 ENIGMA criterion applicability table
Sources
BP2 VCEPThe BRCA2 ENIGMA specification marks BP2 as not applicable in this framework. Details ▾Hide ▴
VCEP rule
Criterion not used by this VCEP framework.
Evidence considered
- BRCA2 ENIGMA criterion applicability table
Sources
BP3 VCEPThe BRCA2 ENIGMA specification marks BP3 as not applicable in this framework. Details ▾Hide ▴
VCEP rule
Criterion not used by this VCEP framework.
Evidence considered
- BRCA2 ENIGMA criterion applicability table
Sources
Identifiers
- Gene
- BRCA2
- Transcript
- NM_000059.3
- Coding (HGVS c.)
- NM_000059.3:c.8149G>T
- Protein (HGVS p.)
- NP_000050.2:p.(Ala2717Ser)
- GRCh38
- chr13:32363351 G>T
- GRCh37
- chr13:32937488 G>T
- ClinVar
- 41564
- COSMIC
- COSV66460731
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…
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
2,248 / 1,614,110 alleles
AF 0.00139 · 2 homozygotes · FAF 0.00164
gnomAD v2.1
315 / 282,680 alleles
AF 0.00111 · 0 homozygotes · FAF 0.00162
By genetic ancestry
gnomAD v4.1
AF 0.0014 · 2248 / 1,614,110 alleles · 2 hom · FAF 0.0016
| European (non-Finnish)2005 / 1,180,000 | 0.00172 hom |
| Admixed American77 / 60,014 | 0.0013 |
| Remaining individuals67 / 62,508 | 0.0011 |
| European (Finnish)65 / 64,022 | 0.001 |
| African/African American33 / 75,026 | 0.00044 |
| Ashkenazi Jewish1 / 29,604 | 3.4e-05 |
0 alternate alleles recorded in 4 other groups: Amish, East Asian, Middle Eastern, South Asian.
gnomAD v2.1
AF 0.0011 · 315 / 282,680 alleles · 0 hom · FAF 0.0016
| Remaining individuals15 / 7,218 | 0.0021 |
| European (non-Finnish)235 / 128,996 | 0.0018 |
| European (Finnish)25 / 25,124 | 0.001 |
| Admixed American32 / 35,440 | 0.0009 |
| African/African American7 / 24,970 | 0.00028 |
| Ashkenazi Jewish1 / 10,364 | 9.6e-05 |
0 alternate alleles recorded in 2 other groups: East Asian, South Asian.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 0.00139272; MAF= 0.13927%, 2248/1614110 alleles, homozygotes = 2) and has highest observed frequency in the European (non-Finnish) population (AF= 0.00169915; MAF= 0.16992%, 2005/1180000 alleles, homozygotes = 2); grpmax FAF= 0.00163682.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.00111433; MAF= 0.11143%, 315/282680 alleles, homozygotes = 0) and has highest observed frequency in the Remaining individuals population (AF= 0.00207814; MAF= 0.20781%, 15/7218 alleles, homozygotes = 0); grpmax FAF= 0.00162114.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.535
- BayesDel
- -0.082
How the predictions were used
PP3 This missense variant lies in the BRCA2 DNA-binding region, but the available computational evidence does not meet the ENIGMA PP3 threshold. The BayesDel no-AF score is -0.0816274, which is below the required threshold of 0.30, and no SpliceAI result showing a score of at least 0.2 was identified. Details ▾Hide ▴
Rule
For BRCA2, PP3 requires BayesDel no-AF >=0.30 for qualifying missense variants in a clinically important domain and/or SpliceAI >=0.2 for predicted splice impact.
Evidence considered
- BayesDel no-AF score -0.0816274
- REVEL score 0.535
- ENIGMA PP3 thresholds
Still missing
- No SpliceAI score was available in the reviewed data.
Sources
BP4 The BayesDel no-AF score is -0.0816274, which is consistent with the benign side of the BRCA2 ENIGMA threshold, but BP4 for a missense variant in a clinically important domain also requires SpliceAI less than or equal to 0.1. Because no SpliceAI result was identified, BP4 is not met from the available data. Details ▾Hide ▴
Rule
For qualifying BRCA2 missense variants in a clinically important domain, BP4 requires BayesDel no-AF <=0.18 and SpliceAI <=0.1.
Evidence considered
- BayesDel no-AF score -0.0816274
- ENIGMA BP4 rule requires BayesDel <=0.18 and SpliceAI <=0.1
Still missing
- No SpliceAI score was available in the reviewed data.
Sources
BP7 RNA evidence curated for this variant reported no aberrant splicing, but the available materials did not provide a direct ENIGMA BP7 assignment for this missense variant. BP7 was therefore not separately assessed. Details ▾Hide ▴
Rule
BP7 is applied under specific ENIGMA RNA-only conditions and was not directly assigned here.
Evidence considered
- ENIGMA Table 9 notes no aberrant splicing for c.8149G>T
Still missing
- No direct BP7 code assignment was identified for this exact variant.
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.03). REVEL score = 0.535. BayesDel score = -0.0816274.
8 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata. None of the listed paper records explicitly indicates that the variant is named.
Recorded publications
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PMID 18375895 ↗Clinical classification of BRCA1 and BRCA2 DNA sequence variants: the value of cytokeratin profiles and evolutionary analysis--a report from the kConFab Investigators.No paper-specific finding is recorded.
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PMID 29394989 ↗Assessment of the Clinical Relevance of BRCA2 Missense Variants by Functional and Computational Approaches.No paper-specific finding is recorded.
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PMID 11802209 ↗Comprehensive analysis of 989 patients with breast or ovarian cancer provides BRCA1 and BRCA2 mutation profiles and frequencies for the German population.No paper-specific finding is recorded.
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PMID 12955716 ↗Analysis of BRCA1 and BRCA2 genes in Spanish breast/ovarian cancer patients: a high proportion of mutations unique to Spain and evidence of founder effects.No paper-specific finding is recorded.
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PMID 19471317 ↗Impact of BRCA1 and BRCA2 variants on splicing: clues from an allelic imbalance study.No paper-specific finding is recorded.
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PMID 20104584 ↗Characterization of BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance in unilateral and bilateral breast cancer: the WECARE study.No paper-specific finding is recorded.
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PMID 21702907 ↗A high-throughput protocol for mutation scanning of the BRCA1 and BRCA2 genes.No paper-specific finding is recorded.
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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
2,248 / 1,614,110 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.030
Open source ↗
ClinVar
22 Benign · 11 Likely benign · 2 Uncertain significance · 1 Likely 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/41564/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/13-32937488-G-T?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr13-32363351-G-T?dataset=gn…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000059.3%3Ac.8149…
- OncoKB ↗www.oncokb.org/gene/BRCA2/A2717S
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=123627240
- 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= 0.00139272; MAF= 0.13927%, 2248/1614110 alleles, homozygotes = 2) and has highest observed frequency in the European (non-Finnish) population (AF= 0.00169915; MAF= 0.16992%, 2005/1180000 alleles, homozygotes = 2); grpmax FAF= 0.00163682.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.00111433; MAF= 0.11143%, 315/282680 alleles, homozygotes = 0) and has highest observed frequency in the Remaining individuals population (AF= 0.00207814; MAF= 0.20781%, 15/7218 alleles, homozygotes = 0); grpmax FAF= 0.00162114.
ClinVar
This variant has been reported in ClinVar as Benign (22 clinical laboratories) and as Likely benign (11 clinical laboratories) and as Uncertain significance (2 clinical laboratories) and as Likely Benign (1 clinical laboratory) and as Benign by ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel, ClinGen (expert panel). (ClinVarID = 41564)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.03). REVEL score = 0.535. BayesDel score = -0.0816274.
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 previously been reported in somatic cancers (COSMIC; COSV66460731, n = 3 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.