About BRCA2
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
BRCA2 c.1274A>G, p.(Glu425Gly)
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. 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
ENIGMA BP1_Strong is met: NM_000059.3:c.1274A>G is a missense variant (p.Glu425Gly) located outside the defined clinically important functional domains (PALB2 binding domain aa 10-40; DNA binding domain aa 2481-3186), and SpliceAI predicts no splicing impact (max delta = 0.00, ≤0.1). Dines et al. 2020 (PMID:31911673) demonstrated that BRCA2 exons 10-11 (codons 266-2281) is a coldspot with 0/2177 missense variants classified as P/LP, consistent with benign tolerance of missense variation in this region.
Recorded classification: Likely benign
ENIGMA BRCA2 VCEP Table 3 combination rules applied. BP1 at Strong strength is the sole met criterion. ENIGMA Table 3 likely-benign rule 5 permits a single Strong (Benign) criterion to reach Likely Benign when it encompasses multiple evidence types (BP1_Strong requires: missense outside clinically important functional domains AND SpliceAI ≤0.1). The points-based scoring system confirms: BP1_Strong = -4 points, which falls in the Likely Benign range (-6 to -2). No pathogenic criteria are met, so no conflicting 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
3 / 1,608,512 alleles
gnomAD v4.1: 3 / 1,608,512 alleles. Recorded AF 1.86508e-06. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 4.10418e-06; MAF= 0.00041%, 1/243654 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 3.48821e-05; MAF= 0.00349%, 1/28668 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
6 reported laboratory submissions
5 Uncertain significance · 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, with the data and sources behind each one.
26 criteria with recorded statuses: 1 met · 16 not met · 0 not assessed · 9 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_000059.3:c.1274A>G (p.Glu425Gly) is a missense variant in BRCA2 exon 10, located outside the ENIGMA-defined clinically important functional domains (PALB2 binding domain aa 10-40; DNA binding domain aa 2481-3186).
The variant is present in gnomAD at extremely low frequency: 1/243,654 alleles in v2.1 and 3/1,608,512 alleles in v4.1 (grpmax FAF=3.71e-06), and is absent from gnomAD-Canada.
SpliceAI predicts no splicing impact (max delta = 0.00). BayesDel no-AF score is -0.421301 and REVEL is 0.13, both in the benign range.
ENIGMA BP1_Strong is met: the variant is a missense substitution outside clinically important functional domains with no predicted splicing impact.
Dines et al. 2020 (PMID:31911673) identified BRCA2 exons 10-11 (codons 266-2281) as a coldspot with 0/2177 missense variants classified as pathogenic or likely pathogenic, consistent with tolerance of missense variation in this region.
The clinical-history likelihood ratio from Li et al. 2020 is 0.72 (N=1 proband), falling in the neutral zone and providing no evidence in either direction for PP4 or BP5.
No functional assay data, segregation data, case-control data, or de novo observations are available for this variant. No published paper mentions this specific variant.
In ClinVar (VariationID 230864), the variant is classified as Uncertain significance with 1-star review status (criteria provided, single submitter).
Using the ENIGMA BRCA2 Table 3 combination rules, BP1_Strong alone is insufficient to reach Likely Benign, which requires either Strong (Benign) + Supporting (Benign), Strong (Benign) + Moderate (Benign), or Moderate (Benign) + Supporting (Benign). The variant is classified as Uncertain Significance.
No criteria match.
Met · 1
BP1 StrongENIGMA BP1_Strong is met: NM_000059.3:c.1274A>G is a missense variant (p.Glu425Gly) located outside the defined clinically important functional domains (PALB2 binding domain aa 10-40; DNA binding domain aa 2481-3186), and SpliceAI predicts no splicing impact (max delta = 0.00, ≤0.1). Dines et al. 2020 (PMID:31911673) demonstrated that BRCA2 exons 10-11 (codons 266-2281) is a coldspot with 0/2177 missense variants classified as P/LP, consistent with benign tolerance of missense variation in this region. Details ▾Hide ▴
Evidence considered
- Missense variant outside ENIGMA clinically important functional domains (codon 425 not in aa 10-40 or aa 2481-3186).
- SpliceAI max delta = 0.00 (no splicing predicted).
- Dines et al. 2020: codon 425 falls within BRCA2 exon 10-11 coldspot region with 0/2177 P/LP missense variants.
Sources
Not met · 16 · evaluated, threshold not reached
PVS1 PVS1 is restricted to null variants (nonsense, frameshift, canonical ±1,2 splice sites, initiation codon, or exon deletions) per ENIGMA BRCA2 specifications. NM_000059.3:c.1274A>G is a missense variant (p.Glu425Gly) and does not qualify. Details ▾Hide ▴
Evidence considered
- Variant is a missense substitution
- not a null variant.
Sources
pvs1_variant_assessmentvcep_specifications_v1_2_2024_11_18
PS1 No previously classified pathogenic or likely pathogenic variant resulting in the same amino acid change (p.Glu425Gly) or a different missense change at codon 425 was identified. The PM5 candidate search for same-residue comparator variants returned no candidates. Details ▾Hide ▴
Evidence considered
- No pathogenic variant at the same codon identified in ClinVar or VCEP databases.
Sources
pm5_candidatesclinvar ↗
PS3 NM_000059.3:c.1274A>G (p.Glu425Gly) was not found in ENIGMA Specifications Table 9 (curated functional assay results) or in Supplementary Table 4 (functional assay results). OncoKB reports unknown oncogenic effect with no variant-specific functional evidence. No published functional studies testing this variant or a systematically characterized range including codon 425 were identified. Details ▾Hide ▴
Evidence considered
- Variant absent from ENIGMA Table 9 curated functional assay results.
- OncoKB reports Unknown Oncogenic Effect.
Still missing
- No functional studies available for this variant.
Sources
vcep_specifications_table9_v1_2_2024_11_18oncokb ↗
PS4 No case-control data demonstrating significantly increased prevalence of this variant in affected individuals compared to controls is available. ENIGMA PS4 requires p-value ≤0.05 and OR ≥4 (lower CI excludes 2.0). Details ▾Hide ▴
Evidence considered
- No case-control study data available.
Still missing
- No case-control data for this variant.
PM2 ENIGMA PM2 applies as Supporting when the variant is absent from gnomAD v2.1 (non-cancer, exome) and v3.1 (non-cancer) controls. NM_000059.3:c.1274A>G is present in gnomAD v2.1 at 1/243,654 alleles (AF=4.1e-6) and in gnomAD v4.1 at 3/1,608,512 alleles (AF=1.9e-6; grpmax FAF=3.71e-6). Presence in controls, even at extremely low frequency, precludes application of PM2 per ENIGMA specifications. Details ▾Hide ▴
Evidence considered
- Variant present in gnomAD v2.1 (1/243
- 654 alleles) and v4.1 (3/1
- 608
- 512 alleles).
Sources
PP1 No co-segregation data are available for this variant. ENIGMA PP1 requires a quantitative co-segregation analysis with LR ≥2.08:1 for Supporting-level evidence. Details ▾Hide ▴
Evidence considered
- No segregation data available.
Still missing
- No co-segregation analysis performed.
PP3 ENIGMA PP3 applies for missense variants when located inside a clinically important functional domain AND BayesDel no-AF ≥0.30, or when SpliceAI ≥0.2. Codon 425 is outside the defined clinically important functional domains (PALB2 binding domain aa 10-40; DNA binding domain aa 2481-3186). BayesDel no-AF is -0.421301 and SpliceAI max delta is 0.00. Neither condition is met. Details ▾Hide ▴
Evidence considered
- BayesDel no-AF = -0.421301.
- SpliceAI max delta = 0.00.
- Codon 425 is outside ENIGMA-defined clinically important functional domains.
Sources
PP4 ENIGMA PP4 uses the clinical-history likelihood ratio from Li et al. 2020 (PMID:31853058). For NM_000059.3:c.1274A>G, the LR is 0.72 (LOG(LR) = -0.325, N_Probands = 1). This falls in the neutral zone (>0.48 and <2.08) and provides no supporting evidence in either direction. Details ▾Hide ▴
Evidence considered
- Clinical-history LR = 0.72 (neutral
- N=1 proband).
Sources
vcep_pmid_31853058_brca2_clinical_history_lrPMID:31853058 ↗
BA1 ENIGMA BA1 requires filter allele frequency (FAF) > 0.1% (FAF > 0.001). The maximum FAF for this variant is 3.71e-06 (0.00037%) in gnomAD v4.1, well below the BA1 threshold. Details ▾Hide ▴
Evidence considered
- grpmax FAF = 3.71e-06 (0.00037%)
- far below BA1 threshold of 0.001.
Sources
BS1 ENIGMA BS1_Strong requires FAF > 0.01% (FAF > 0.0001) and BS1_Supporting requires FAF > 0.002% (FAF > 0.00002). The maximum FAF for this variant is 3.71e-06 (0.00037%), which is below both thresholds. Details ▾Hide ▴
Evidence considered
- grpmax FAF = 3.71e-06 (0.00037%)
- below BS1_Supporting threshold of 0.00002.
Sources
BS2 ENIGMA BS2 requires observation in healthy adults without Fanconi Anemia phenotype, scored via a points system per proband. No proband-level data with documented absence of Fanconi Anemia features are available for this variant. Details ▾Hide ▴
Evidence considered
- No proband-level data with documented absence of Fanconi Anemia phenotype.
Still missing
- No proband phenotypes available for BS2 assessment.
BS3 NM_000059.3:c.1274A>G was not found in ENIGMA Specifications Table 9 (curated functional assay results showing no damaging effect). No published well-established functional studies demonstrating no damaging effect on protein function were identified for this variant. Details ▾Hide ▴
Evidence considered
- Variant absent from ENIGMA Table 9 functional assay results.
Still missing
- No functional studies showing no damaging effect.
Sources
vcep_specifications_table9_v1_2_2024_11_18
BS4 No lack-of-segregation data are available for this variant. ENIGMA BS4 requires a quantitative co-segregation analysis showing LR ≤0.48:1 for Supporting-level evidence. Details ▾Hide ▴
Evidence considered
- No segregation data available.
Still missing
- No co-segregation analysis showing lack of segregation.
BP4 ENIGMA BP4 applies only to missense variants located inside a clinically important functional domain with no predicted impact via protein change or splicing (BayesDel no-AF ≤0.18 AND SpliceAI ≤0.1). Codon 425 is outside the defined clinically important functional domains (PALB2 binding domain aa 10-40; DNA binding domain aa 2481-3186), so the ENIGMA BP4 rule precondition is not satisfied. Computational predictors are assessed under PP3/BP1 instead. Details ▾Hide ▴
Evidence considered
- Codon 425 is outside ENIGMA-defined clinically important functional domains.
- BayesDel no-AF = -0.421301
- SpliceAI = 0.00.
Sources
bayesdelspliceai ↗
BP5 ENIGMA BP5 uses the clinical-history likelihood ratio from Li et al. 2020 (PMID:31853058). For NM_000059.3:c.1274A>G, the LR is 0.72. BP5_Supporting requires LR ≤0.48; the variant's LR falls in the neutral zone and does not support benignity. Details ▾Hide ▴
Evidence considered
- Clinical-history LR = 0.72 (neutral
- does not meet BP5_Supporting threshold of ≤0.48).
Sources
vcep_pmid_31853058_brca2_clinical_history_lrPMID:31853058 ↗
BP7 ENIGMA BP7_Strong (RNA) requires well-established functional studies showing no damaging effect at the mRNA transcript level. BP7_Supporting applies only to silent or intronic variants. No functional RNA studies are available for this missense variant. Although the variant is located outside clinically important domains, the mRNA functional data prerequisite is not met. Details ▾Hide ▴
Evidence considered
- No mRNA transcript studies available for this variant.
Still missing
- No mRNA functional studies for this variant.
Not applicable · 9· recorded as not applicable Show reasons ▾Hide reasons ▴
PS2 VCEPPS2 is marked Not Applicable by the ENIGMA BRCA2 VCEP specification. Details ▾Hide ▴
Sources
PM1 VCEPPM1 is marked Not Applicable by the ENIGMA BRCA2 VCEP specification; considered as component of bioinformatic analysis (PP3/BP4) instead. Details ▾Hide ▴
Sources
PM5 N/AENIGMA repurposes PM5 for protein termination codon (PTC) variants only (PM5_PTC). NM_000059.3:c.1274A>G is a missense variant and does not qualify for PM5_PTC. Classic same-residue missense PM5 is not applicable in the ENIGMA BRCA2 framework. Details ▾Hide ▴
Evidence considered
- Variant is missense
- PM5_PTC only applicable to PTC variants per ENIGMA.
Sources
pm5_candidatesvcep_specifications_table4_v1_2_2024_11_18
PM6 VCEPPM6 is marked Not Applicable by the ENIGMA BRCA2 VCEP specification. Details ▾Hide ▴
Sources
PP2 VCEPPP2 is marked Not Applicable by the ENIGMA BRCA2 VCEP specification. Details ▾Hide ▴
Sources
PP5 VCEPPP5 is marked Not Applicable by the ENIGMA BRCA2 VCEP specification. ClinVar classification is Uncertain significance with 1-star review status (criteria provided, single submitter); the PP5/BP6 3-star expert panel override does not apply. Details ▾Hide ▴
BP2 VCEPBP2 is marked Not Applicable by the ENIGMA BRCA2 VCEP specification. Details ▾Hide ▴
Sources
BP6 VCEPBP6 is marked Not Applicable by the ENIGMA BRCA2 VCEP specification. ClinVar review status is 1-star, not 3-star expert panel, so the PP5/BP6 override does not apply. Details ▾Hide ▴
PS5 N/APS5 is not an ENIGMA BRCA2 VCEP criterion. ClinVar review status is 1-star (criteria provided, single submitter), not 3-star expert panel, so the PP5/BP6 override does not apply. Details ▾Hide ▴
Identifiers
- Gene
- BRCA2
- Transcript
- NM_000059.3
- Coding (HGVS c.)
- NM_000059.3:c.1274A>G
- Protein (HGVS p.)
- NP_000050.2:p.(Glu425Gly)
- GRCh38
- chr13:32332752 A>G
- GRCh37
- chr13:32906889 A>G
- ClinVar
- 230864
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
3 / 1,608,512 alleles
AF 1.87e-06 · 0 homozygotes · FAF 3.71e-06
gnomAD v2.1
1 / 243,654 alleles
AF 4.1e-06 · 0 homozygotes
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 1.9e-06 · 3 / 1,608,512 alleles · 0 hom · FAF 3.7e-06
| South Asian2 / 89,540 | 2.2e-05 |
| African/African American1 / 74,584 | 1.3e-05 |
0 alternate alleles recorded in 8 other groups: Remaining individuals, Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, Ashkenazi Jewish, European (non-Finnish).
gnomAD v2.1
AF 4.1e-06 · 1 / 243,654 alleles · 0 hom
| South Asian1 / 28,668 | 3.5e-05 |
0 alternate alleles recorded in 7 other groups: African/African American, Admixed American, Ashkenazi Jewish, East Asian, European (Finnish), European (non-Finnish), Remaining individuals.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 1.86508e-06; MAF= 0.00019%, 3/1608512 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 2.23364e-05; MAF= 0.00223%, 2/89540 alleles, homozygotes = 0); grpmax FAF= 3.71e-06.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 4.10418e-06; MAF= 0.00041%, 1/243654 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 3.48821e-05; MAF= 0.00349%, 1/28668 alleles, homozygotes = 0).
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.130
- BayesDel
- -0.421
How the predictions were used
PP3 ENIGMA PP3 applies for missense variants when located inside a clinically important functional domain AND BayesDel no-AF ≥0.30, or when SpliceAI ≥0.2. Codon 425 is outside the defined clinically important functional domains (PALB2 binding domain aa 10-40; DNA binding domain aa 2481-3186). BayesDel no-AF is -0.421301 and SpliceAI max delta is 0.00. Neither condition is met. Details ▾Hide ▴
Evidence considered
- BayesDel no-AF = -0.421301.
- SpliceAI max delta = 0.00.
- Codon 425 is outside ENIGMA-defined clinically important functional domains.
Sources
BP4 ENIGMA BP4 applies only to missense variants located inside a clinically important functional domain with no predicted impact via protein change or splicing (BayesDel no-AF ≤0.18 AND SpliceAI ≤0.1). Codon 425 is outside the defined clinically important functional domains (PALB2 binding domain aa 10-40; DNA binding domain aa 2481-3186), so the ENIGMA BP4 rule precondition is not satisfied. Computational predictors are assessed under PP3/BP1 instead. Details ▾Hide ▴
Evidence considered
- Codon 425 is outside ENIGMA-defined clinically important functional domains.
- BayesDel no-AF = -0.421301
- SpliceAI = 0.00.
Sources
bayesdelspliceai ↗
BP7 ENIGMA BP7_Strong (RNA) requires well-established functional studies showing no damaging effect at the mRNA transcript level. BP7_Supporting applies only to silent or intronic variants. No functional RNA studies are available for this missense variant. Although the variant is located outside clinically important domains, the mRNA functional data prerequisite is not met. Details ▾Hide ▴
Evidence considered
- No mRNA transcript studies available for this variant.
Still missing
- No mRNA functional studies for this variant.
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.13. BayesDel score = -0.421301.
8 paper records listed. 1 cited in the classification. None of the listed paper records explicitly indicates that the variant is named.
Cited in the classification
-
PMID 31911673 ↗Systematic misclassification of missense variants in BRCA1 and BRCA2 "coldspots".Dines JN et al. · 2020 MayEvaluated BRCA1 and BRCA2 missense variants in ClinVar to identify coldspots. BRCA2 exons 10-11 (codons 266-2281) were identified as coldspots with 0 of 2177 missense variants classified as pathogenic or likely pathogenic, compared to 110 benign/likely benign and 2067 VUS. The odds ratio of pathogenicity for BRCA2 exon 10-11 was <0.05, translating to strong benign per ACMG/AMP Bayesian framework.→ BP1 Does not name this variant
Source detail
Exon 10 and 11 in BRCA2 were considered potential coldspots, consistent with literature describing the lack of pathogenic missense variants outside of known critical domains.
Location Results, Table 1; Figure 1
Other recorded publications
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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.Provides the ACMG/AMP standards and guidelines for interpretation of sequence variants, including the criteria framework and combination rules for variant classification. Serves as the foundational methodology reference; does not discuss BRCA2 c.1274A>G or any specific variant.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. · 2007American Cancer Society guidelines for breast screening with MRI. Provides breast cancer screening recommendations for women at elevated risk; does not discuss individual variants.Does not name this variant
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PMID 20301471 ↗Wilms Tumor Predisposition.Adam MP et al. · 1993GeneReviews entry on Wilms Tumor Predisposition, discussing WT1 and related genes. Not relevant to BRCA2 variant assessment.Does not name this variant
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PMID 24366376 ↗Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women: U.S. Preventive Services Task Force recommendation statement.USPSTF recommendation statement on genetic risk assessment, counseling, and BRCA testing for breast and ovarian cancer susceptibility. Provides population-level screening guidelines; does not discuss individual variants or NM_000059.3:c.1274A>G.Does not name this variant
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PMID 24366402 ↗Summaries for patients. Assessing the genetic risk for BRCA-related breast or ovarian cancer in women: recommendations from the U.S. Preventive Services Task Force.Patient summary of the USPSTF recommendations on BRCA-related cancer genetic risk assessment. Lay-language summary; does not discuss individual variants.Does not name this variant
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PMID 24493721 ↗American Society of Clinical Oncology Expert Statement: collection and use of a cancer family history for oncology providers.ASCO expert statement on collection and use of cancer family history for oncology providers. Provides clinical guidance on family history documentation; does not discuss individual BRCA2 variants or NM_000059.3:c.1274A>G.Does not name this variant
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PMID 28492532 ↗Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.Describes the Sherloc refinement of the ACMG-AMP variant classification criteria, providing a systematic framework for evidence weighting. Does not discuss BRCA2 c.1274A>G or any specific 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
3 / 1,608,512 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
5 Uncertain significance · 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/230864/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/13-32906889-A-G?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr13-32332752-A-G?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/13-32332752-A-G
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000059.3%3Ac.1274…
- OncoKB ↗www.oncokb.org/gene/BRCA2/E425G
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=BRCA2+c.1274A%3EG
- 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= 1.86508e-06; MAF= 0.00019%, 3/1608512 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 2.23364e-05; MAF= 0.00223%, 2/89540 alleles, homozygotes = 0); grpmax FAF= 3.71e-06.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 4.10418e-06; MAF= 0.00041%, 1/243654 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 3.48821e-05; MAF= 0.00349%, 1/28668 alleles, homozygotes = 0).
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Uncertain significance (5 clinical laboratories) and as Uncertain Significance (1 clinical laboratory). (ClinVarID = 230864)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.13. BayesDel score = -0.421301.
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.