About BRCA2
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
BRCA2 c.6698C>A, p.(Ala2233Asp)
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: 3
Pathogenic criteria applied · 0
No pathogenic criterion marked as applied in the recorded assessment.
Benign criteria applied · 3
BS4Moderate
BS4 · moderate
Parsons et al. 2019 (PMID:31131967) multifactorial likelihood analysis yields a combined LR of 0.177 (posterior probability 0.0036, IARC Class 2 — Likely Benign). This meets the BS4_Moderate threshold (LR ≤0.23). The analysis integrates co-occurrence LR (1.13) and family history LR (0.16) across multiple data sources.
BP1Strong
BP1 · strong
Missense variant at codon 2233 lies outside both ENIGMA-defined clinically important functional domains (PALB2 binding domain aa 10-40 and DNA binding domain aa 2481-3186). SpliceAI max delta = 0.0 (≤0.1), confirming no predicted splicing impact. Meets ENIGMA BP1_Strong criteria.
BP5Supporting
BP5 · supporting
Li et al. 2020 (PMID:31853058) clinical history likelihood ratio is 0.3604 (based on 7 probands), meeting the ENIGMA BP5_Supporting threshold of LR ≤0.48. This indicates the personal and family cancer history of carriers is more consistent with a benign variant than a pathogenic BRCA2 variant.
Recorded classification: Likely benign
No pathogenic criteria are met. Three benign criteria are met: BP1_Strong (missense outside clinically important functional domains, SpliceAI delta=0.0), BS4_Moderate (Parsons et al. 2019 multifactorial combined LR=0.177, IARC Class 2), and BP5_Supporting (Li et al. 2020 clinical history LR=0.3604). Per ENIGMA BRCA1/BRCA2 Specification v1.2 Table 3, the combination of 1 Strong Benign + 1 Supporting Benign satisfies the Likely Benign classification rule. BS4_Moderate provides additional corroborating evidence.
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
31 / 1,613,926 alleles
gnomAD v4.1: 31 / 1,613,926 alleles. Recorded AF 1.92078e-05. Recorded homozygote count 1.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 7.95906e-06; MAF= 0.00080%, 2/251286 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 6.15839e-05; MAF= 0.00616%, 1/16238 alleles, homozygotes = 0).
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
No listed criterion applied
SpliceAI score
0.000 maximum delta
Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.
No listed criterion applied
SpliceAI ↗
ClinVar submissions
9 reported laboratory submissions
6 Uncertain significance · 2 Likely benign · 1 Uncertain Significance. 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 v1.2.0, with the data and sources behind each one.
29 criteria with recorded statuses: 3 met · 6 not met · 5 not assessed · 15 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
BRCA2 c.6698C>A (p.Ala2233Asp) is a missense variant in exon 11, located at amino acid 2233, which is outside both ENIGMA-defined clinically important functional domains (PALB2 binding domain aa 10-40 and DNA binding domain aa 2481-3186). SpliceAI predicts no splicing impact (max delta = 0.0). This meets BP1_Strong per ENIGMA v1.2 specifications.
In a large-scale multifactorial likelihood analysis by Parsons et al. 2019 (PMID:31131967), this variant received a combined likelihood ratio of 0.177 and posterior probability of pathogenicity of 0.0036, corresponding to IARC Class 2 (Likely Benign). This meets BS4_Moderate (LR ≤0.23).
Clinical history likelihood ratio analysis by Li et al. 2020 (PMID:31853058), based on 7 probands, yielded an LR of 0.3604, meeting BP5_Supporting (LR ≤0.48). The personal and family cancer history of carriers is more consistent with a benign variant than a pathogenic BRCA2 variant.
The variant is present at very low frequency in gnomAD (v2.1: 2/251,286 alleles; v4.1: 31/1,613,926 alleles including 1 homozygote), which is insufficient for BA1 or BS1 but also precludes PM2_Supporting. No variant-specific functional assay data are available in ENIGMA Table 9.
Combining criteria per ENIGMA Table 3: BP1_Strong + BS4_Moderate satisfies the Likely Benign combination rule (1 Strong Benign + 1 Moderate Benign). BP5_Supporting provides additional corroborating benign evidence. No pathogenic criteria are met.
No criteria match.
Met · 3
BS4 ModerateParsons et al. 2019 (PMID:31131967) multifactorial likelihood analysis yields a combined LR of 0.177 (posterior probability 0.0036, IARC Class 2 — Likely Benign). This meets the BS4_Moderate threshold (LR ≤0.23). The analysis integrates co-occurrence LR (1.13) and family history LR (0.16) across multiple data sources. Details ▾Hide ▴
Evidence considered
- Parsons et al. 2019 SuppT1: Combined LR = 0.177
- Posterior probability = 0.0036
- IARC Class 2 (Likely Benign).
- ENIGMA ST7 Reference Set: Prior probability 0.02
- Posterior probability 0.0036
- IARC Class 2.
- Co-occurrence LR = 1.13
- Family history LR = 0.16.
Sources
BP1 StrongMissense variant at codon 2233 lies outside both ENIGMA-defined clinically important functional domains (PALB2 binding domain aa 10-40 and DNA binding domain aa 2481-3186). SpliceAI max delta = 0.0 (≤0.1), confirming no predicted splicing impact. Meets ENIGMA BP1_Strong criteria. Details ▾Hide ▴
Evidence considered
- A2233D at aa 2233
- outside PALB2 binding domain (aa 10-40) and DNA binding domain (aa 2481-3186).
- SpliceAI max delta score = 0.00
- no splicing impact predicted.
Sources
BP5 SupportingLi et al. 2020 (PMID:31853058) clinical history likelihood ratio is 0.3604 (based on 7 probands), meeting the ENIGMA BP5_Supporting threshold of LR ≤0.48. This indicates the personal and family cancer history of carriers is more consistent with a benign variant than a pathogenic BRCA2 variant. Details ▾Hide ▴
Evidence considered
- Li et al. 2020 clinical history LR = 0.3604
- based on 7 probands.
- Meets BP5_Supporting threshold (LR ≤0.48).
Sources
vcep_pmid_31853058_brca2_clinical_history_lrPMID:31853058 ↗
Not met · 6 · evaluated, threshold not reached
PS1 No previously classified pathogenic or likely pathogenic missense variant at BRCA2 codon 2233 (Ala) was identified in ENIGMA reference sets or ClinVar. PS1 requires a different amino acid change at the same residue to have been established as pathogenic. Details ▾Hide ▴
Evidence considered
- Comprehensive search of ENIGMA ST7 Reference Set and Parsons et al. 2019 SuppT1 identified no pathogenic comparator variant at codon 2233.
Sources
pm5_candidatesvcep_supplementarytables_v1_2_2024_11_18
PS4 The combined multifactorial likelihood ratio from Parsons et al. 2019 is 0.177, which is in the benign direction and does not support pathogenicity. No case-control study demonstrates significantly increased prevalence of this variant in affected individuals (OR ≥4 required). Details ▾Hide ▴
Evidence considered
- Parsons et al. 2019 multifactorial analysis: Combined LR = 0.177 (odds for causality)
- IARC Class = Likely Benign.
Sources
vcep_humu_40_1557_s001PMID:31131967 ↗
PM2 ENIGMA PM2_Supporting requires absence from controls in gnomAD outbred populations. This variant is present in gnomAD v2.1 (2/251,286 alleles; AF=7.96e-06) and v4.1 (31/1,613,926 alleles; AF=1.92e-05), including one homozygote in v4.1. Details ▾Hide ▴
Evidence considered
- Variant present in gnomAD v2.1 (2 alleles) and v4.1 (31 alleles
- 1 homozygote). Does not meet PM2_Supporting absence requirement.
Sources
PP4 Li et al. 2020 (PMID:31853058) clinical history likelihood ratio is 0.3604, which falls below the PP4_Supporting threshold of LR ≥2.08. This LR is in the benign direction and instead supports BP5. Details ▾Hide ▴
Evidence considered
- Clinical history LR = 0.3604 (7 probands). Not in PP4 range (LR ≥2.08).
Sources
vcep_pmid_31853058_brca2_clinical_history_lrPMID:31853058 ↗
BA1 gnomAD v4.1 grpmax filter allele frequency (FAF) is 1.53e-05 (0.00153%), far below the ENIGMA BA1 threshold of FAF >0.1% (0.001). Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 grpmax FAF = 1.533e-05. Far below BA1 threshold of 0.001.
Sources
BS1 gnomAD v4.1 grpmax FAF = 1.53e-05 (0.00153%) is below even the BS1_Supporting threshold of FAF >0.002% (0.00002). The variant is too rare in population databases to apply BS1. Details ▾Hide ▴
Not assessed · 5 · no assessment recorded
PS3 No variant-specific functional assay data found in ENIGMA Specifications Table 9 or in published literature. The variant falls outside the clinically important functional domains (DNA binding domain aa 2481-3186, PALB2 binding domain aa 10-40), where calibrated functional assays are primarily concentrated. Details ▾Hide ▴
Evidence considered
- ENIGMA Table 9 contains no entry for c.6698C>A. OncoKB classifies this variant as Unknown Oncogenic Effect with no variant-specific functional evidence.
Still missing
- No calibrated mammalian functional assay data available for this specific missense variant.
Sources
vcep_specifications_table9_v1_2_2024_11_18oncokb ↗
PP1 No co-segregation data available for this variant. Co-segregation analysis requires quantitative LR from family studies. Details ▾Hide ▴
Evidence considered
- No co-segregation data identified in ENIGMA resources or literature.
Still missing
- No family-based co-segregation analysis available.
BS2 One homozygote is observed in gnomAD v4.1 (31 total alleles), but no phenotypic data are available to determine whether this individual lacked features of Fanconi Anemia, as required by ENIGMA BS2. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1: 1 homozygote among 31 carriers. No FA phenotype data available.
Still missing
- Phenotypic data for the gnomAD v4.1 homozygote is unavailable. If confirmed healthy adult without Fanconi Anemia
- BS2 could apply.
Sources
BS3 No variant-specific functional assay data found in ENIGMA Specifications Table 9. The variant is outside the clinically important functional domains where calibrated functional assays are concentrated. Details ▾Hide ▴
Evidence considered
- ENIGMA Table 9 contains no entry for c.6698C>A.
Still missing
- No calibrated functional assay data available for this variant.
Sources
vcep_specifications_table9_v1_2_2024_11_18
BP7 BP7_Strong (RNA) requires well-established mRNA assay data showing no damaging effect on transcript profile. No allele-specific mRNA splicing assay has been performed for this variant. The variant is a missense outside functional domains, making it eligible for BP7_Strong (RNA) if mRNA data were available. Details ▾Hide ▴
Evidence considered
- No mRNA assay data identified in ENIGMA supplementary tables or literature for c.6698C>A.
Still missing
- mRNA transcript analysis data not available for this variant.
Sources
Not applicable · 15· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/AMissense variant (c.6698C>A, p.Ala2233Asp); PVS1 applies only to null variants (nonsense, frameshift, canonical ±1,2 splice sites, initiation codon, or exon deletions). Details ▾Hide ▴
Evidence considered
- Missense substitution in exon 11 of BRCA2 does not meet PVS1 null-variant criteria.
Sources
pvs1_variant_assessment
PS2 VCEPNot applicable for this VCEP per ClinGen ENIGMA BRCA1/BRCA2 Specification v1.2. Details ▾Hide ▴
Sources
PM1 VCEPNot applicable per ENIGMA BRCA1/BRCA2 Specification v1.2. PM1 is considered a component of bioinformatic analysis (PP3/BP4) and is not applied independently. Details ▾Hide ▴
Sources
PM3 N/ARequires co-occurrence with a second pathogenic variant in trans in a Fanconi Anemia proband; no such data available for this missense variant. Details ▾Hide ▴
No further detail was recorded.
PM4 VCEPProtein length changes (in-frame deletions/insertions, stop-loss) only; this is a missense substitution. Details ▾Hide ▴
No further detail was recorded.
PM5 N/AENIGMA repurposes PM5 for protein termination codon (PTC) variants only (PM5_PTC). This is a missense variant, not a PTC. Details ▾Hide ▴
Evidence considered
- Variant class is missense
- PM5_PTC logic does not apply.
Sources
pm5_candidatescspec ↗
PM6 VCEPNot applicable per ENIGMA BRCA1/BRCA2 Specification v1.2. Details ▾Hide ▴
Sources
PP2 VCEPNot applicable per ENIGMA BRCA1/BRCA2 Specification v1.2. Details ▾Hide ▴
Sources
PP3 N/AENIGMA PP3 requires either (a) missense inside a clinically important functional domain with BayesDel no-AF ≥0.30, or (b) SpliceAI ≥0.2 for any missense variant. A2233D at aa 2233 is outside both the PALB2 binding domain (aa 10-40) and DNA binding domain (aa 2481-3186). BayesDel no-AF = 0.15 (<0.30). SpliceAI max delta = 0.0 (<0.2). Neither condition is met. Details ▾Hide ▴
Evidence considered
- Variant at aa 2233 outside functional domains. BayesDel no-AF=0.15
- SpliceAI delta=0.0
- REVEL=0.602 (but ENIGMA PP3 uses BayesDel as the primary protein predictor).
Sources
PP5 VCEPNot applicable for this VCEP per ClinGen ENIGMA BRCA1/BRCA2 Specification v1.2. This criterion is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Details ▾Hide ▴
Sources
BP2 VCEPNot applicable per ENIGMA BRCA1/BRCA2 Specification v1.2. Details ▾Hide ▴
Sources
BP3 VCEPIn-frame deletions/insertions in repetitive regions only; this is a missense substitution. Details ▾Hide ▴
No further detail was recorded.
BP4 N/AENIGMA BP4 requires the variant to be inside a clinically important functional domain (PALB2 binding aa 10-40 or DNA binding aa 2481-3186). A2233D at aa 2233 is outside both domains. Additionally, BayesDel no-AF = 0.15 does not independently trigger BP4. Details ▾Hide ▴
Evidence considered
- Variant at aa 2233
- outside PALB2 binding (10-40) and DNA binding (2481-3186) domains. BayesDel=0.15
- SpliceAI=0.0.
Sources
BP6 VCEPNot applicable per ENIGMA BRCA1/BRCA2 Specification v1.2. Details ▾Hide ▴
Sources
PS5 N/ANot applicable for this VCEP per ClinGen ENIGMA BRCA1/BRCA2 Specification v1.2. Details ▾Hide ▴
Sources
Identifiers
- Gene
- BRCA2
- Transcript
- NM_000059.4
- Coding (HGVS c.)
- NM_000059.4:c.6698C>A
- Protein (HGVS p.)
- NP_000050.3:p.(Ala2233Asp)
- GRCh38
- chr13:32341053 C>A
- GRCh37
- chr13:32915190 C>A
- ClinVar
- 52159
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
31 / 1,613,926 alleles
AF 1.92e-05 · 1 homozygotes · FAF 1.53e-05
gnomAD v2.1
2 / 251,286 alleles
AF 7.96e-06 · 0 homozygotes
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 1.9e-05 · 31 / 1,613,926 alleles · 1 hom · FAF 1.5e-05
| Remaining individuals4 / 62,492 | 6.4e-05 |
| European (non-Finnish)26 / 1,179,920 | 2.2e-051 hom |
| African/African American1 / 75,026 | 1.3e-05 |
0 alternate alleles recorded in 7 other groups: Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish.
gnomAD v2.1
AF 8e-06 · 2 / 251,286 alleles · 0 hom
| African/African American1 / 16,238 | 6.2e-05 |
| European (non-Finnish)1 / 113,638 | 8.8e-06 |
0 alternate alleles recorded in 6 other groups: 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= 1.92078e-05; MAF= 0.00192%, 31/1613926 alleles, homozygotes = 1) and has highest observed frequency in the Remaining individuals population (AF= 6.40082e-05; MAF= 0.00640%, 4/62492 alleles, homozygotes = 0); grpmax FAF= 1.533e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 7.95906e-06; MAF= 0.00080%, 2/251286 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 6.15839e-05; MAF= 0.00616%, 1/16238 alleles, homozygotes = 0).
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.602
- BayesDel
- 0.150
How the predictions were used
BP7 BP7_Strong (RNA) requires well-established mRNA assay data showing no damaging effect on transcript profile. No allele-specific mRNA splicing assay has been performed for this variant. The variant is a missense outside functional domains, making it eligible for BP7_Strong (RNA) if mRNA data were available. Details ▾Hide ▴
Evidence considered
- No mRNA assay data identified in ENIGMA supplementary tables or literature for c.6698C>A.
Still missing
- mRNA transcript analysis data not available for this variant.
Sources
PP3 N/AENIGMA PP3 requires either (a) missense inside a clinically important functional domain with BayesDel no-AF ≥0.30, or (b) SpliceAI ≥0.2 for any missense variant. A2233D at aa 2233 is outside both the PALB2 binding domain (aa 10-40) and DNA binding domain (aa 2481-3186). BayesDel no-AF = 0.15 (<0.30). SpliceAI max delta = 0.0 (<0.2). Neither condition is met. Details ▾Hide ▴
Evidence considered
- Variant at aa 2233 outside functional domains. BayesDel no-AF=0.15
- SpliceAI delta=0.0
- REVEL=0.602 (but ENIGMA PP3 uses BayesDel as the primary protein predictor).
Sources
BP4 N/AENIGMA BP4 requires the variant to be inside a clinically important functional domain (PALB2 binding aa 10-40 or DNA binding aa 2481-3186). A2233D at aa 2233 is outside both domains. Additionally, BayesDel no-AF = 0.15 does not independently trigger BP4. Details ▾Hide ▴
Evidence considered
- Variant at aa 2233
- outside PALB2 binding (10-40) and DNA binding (2481-3186) domains. BayesDel=0.15
- SpliceAI=0.0.
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.602. BayesDel score = 0.149919.
9 paper records listed. 2 cited in the classification.
Cited in the classification
-
PMID 31131967 ↗Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification.Parsons MT et al. · 2019 SepVariant c.6698C>A (p.Ala2233Asp) included in large-scale BRCA2 multifactorial likelihood analysis. Combined LR = 0.177; posterior probability = 0.0036; IARC Class 2 (Likely Benign). Co-occurrence LR = 1.13, family history LR = 0.16.→ BS4 Names this variant
Source detail
Not present in main text; variant-level data extracted from SuppT1 spreadsheet.
Location Supplementary Table 1 (SuppT1), row for c.6698C>A
-
PMID 31853058 ↗Li et al. 2020 BRCA1/2 clinical-history likelihood-ratio modelVariant c.6698C>A included in clinical history likelihood ratio analysis. LOG(LR) = -1.02, LR = 0.36 based on 7 probands. The personal and family cancer history of carriers is more consistent with a benign variant.→ BP5 Names this variant
Source detail
Not present in main text; variant-level data extracted from clinical history LR spreadsheet.
Location Supplementary MOESM3 table (converted to PMID_31853058_BRCA2_clinical_history_LR.xlsx), row for BRCA2 c.6698C>A
Other recorded publications
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PMID 18724707 ↗Computational and structural investigation of deleterious functional SNPs in breast cancer BRCA2 gene.Rajasekaran R et al. · 2008A2233D (BRCA2 p.Ala2233Asp) predicted as 'Not damaged' with a SIFT score of 0.00 in a computational analysis of BRCA2 nsSNPs using SIFT, PolyPhen, and structural modeling.Names this variant
Quoted passage
A2233D 0.00 Not damaged
Results section, SNP prediction table (rs169548, A2233D entry)
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PMID 25682074 ↗Prevalence of BRCA1 and BRCA2 germline mutations in patients with triple-negative breast cancer.Wong-Brown MW et al. · 2015Prevalence study of BRCA1 and BRCA2 germline mutations in triple-negative breast cancer patients. c.6698C>A was not identified among the reported variants.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.ACMG/AMP standards and guidelines for sequence variant interpretation. Does not discuss any specific BRCA2 variant.Does not name this variant
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PMID 31911673 ↗Systematic misclassification of missense variants in BRCA1 and BRCA2 "coldspots".Dines JN et al. · 2020Analyzed BRCA1 and BRCA2 missense variants to identify coldspots — regions tolerant to missense variation. BRCA2 exon 10 and 11 (aa 266-2281) identified as a coldspot with 0 pathogenic variants among 2,177 missense variants. c.6698C>A (p.Ala2233Asp) falls within this coldspot region.Does not name this variant
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PMID 10923033 ↗The breast cancer information core: database design, structure, and scope.Szabo C et al. · 2000Describes the design and structure of the Breast Cancer Information Core (BIC) database. Does not discuss any specific BRCA2 variant.Does not name this variant
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PMID 12692171 ↗American Society of Clinical Oncology policy statement update: genetic testing for cancer susceptibility.ASCO policy statement update on genetic testing for cancer susceptibility. Does not discuss any specific BRCA2 variant.Does not name this variant
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PMID 18163131 ↗The emerging landscape of breast cancer susceptibility.Review of the genetic landscape of breast cancer susceptibility. Does not discuss any specific BRCA2 variant.Does not name this variant
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PMID 28492532 ↗Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.Sherloc refinement of ACMG-AMP variant classification criteria. Does not discuss any specific BRCA2 variant.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
31 / 1,613,926 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.000
Open source ↗
ClinVar
6 Uncertain significance · 2 Likely benign · 1 Uncertain Significance
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/52159/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/13-32915190-C-A?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr13-32341053-C-A?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/13-32341053-C-A
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000059.4%3Ac.6698…
- OncoKB ↗www.oncokb.org/gene/BRCA2/A2233D
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=BRCA2+c.6698C%3EA
- 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= 1.92078e-05; MAF= 0.00192%, 31/1613926 alleles, homozygotes = 1) and has highest observed frequency in the Remaining individuals population (AF= 6.40082e-05; MAF= 0.00640%, 4/62492 alleles, homozygotes = 0); grpmax FAF= 1.533e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 7.95906e-06; MAF= 0.00080%, 2/251286 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 6.15839e-05; MAF= 0.00616%, 1/16238 alleles, homozygotes = 0).
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Uncertain significance (6 clinical laboratories) and as Likely benign (2 clinical laboratories) and as Uncertain Significance (1 clinical laboratory). (ClinVarID = 52159)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.602. BayesDel score = 0.149919.
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.