About BRCA2
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
BRCA2 c.1501A>G, p.(Ile501Val)
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: 1
Benign evidence criteria: 1
Pathogenic criteria applied · 1
PM2Supporting
PM2 · supporting
The variant is absent from gnomAD v2.1 (non-cancer, exome). In gnomAD v4.1, it is observed as a single allele (AF=6.27e-07, 1/1,595,636) in the European (non-Finnish) population. Per ENIGMA guidance, a single observation in a gnomAD outbred population is not informative and does not preclude PM2_Supporting. The variant is also absent from gnomAD-Canada.
Benign criteria applied · 1
BP1Strong
BP1 · strong
ENIGMA BP1_Strong applies to missense variants outside a (potentially) clinically important functional domain with no predicted splicing impact (SpliceAI ≤ 0.1). This missense variant (p.Ile501Val) is at amino acid position 501, which is outside both BRCA2 clinically important functional domains (PALB2 binding: aa 10-40; DNA binding: aa 2481-3186). SpliceAI max delta is 0.0, indicating no splicing impact. BRCA2 exons 10 and 11 (codons 266-2281) contain 0 P/LP missense variants among 2,177 submitted to ClinVar, consistent with this region being a validated coldspot.
Recorded classification: Likely benign
ENIGMA BRCA2 VCEP v1.2.0 conflicting-evidence point system: PM2_Supporting (+1 pathogenic point) and BP1_Strong (-4 benign point) = -3 total points, which falls in the Likely Benign range (-6 to -2). Both pathogenic and benign criteria are met, triggering the ENIGMA Table 3 point-based conflicting evidence rule.
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
1 / 1,595,636 alleles
gnomAD v4.1: 1 / 1,595,636 alleles. Recorded AF 6.26709e-07. Recorded homozygote count 0.
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
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
5 reported laboratory submissions
4 Uncertain significance · 1 Likely benign. ClinVar API review status: criteria provided, conflicting classifications.
Context only
ClinVar ↗
Functional evidence
Statement recorded
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. BRCA2, a tumor suppressor involved in the DNA damage response, is mutated in various cancer types.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
No matching record reported
This variant has not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under ClinGen BRCA2 VCEP v1.2.0, with the data and sources behind each one.
26 criteria with recorded statuses: 2 met · 14 not met · 0 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
BP1_Strong is met: c.1501A>G (p.Ile501Val) is a missense variant located at amino acid 501, outside both BRCA2 clinically important functional domains (PALB2 binding aa 10-40; DNA binding aa 2481-3186), with no predicted splicing impact (SpliceAI max delta 0.0).
PM2_Supporting is met: the variant is absent from gnomAD v2.1 (non-cancer, exome) and observed as a single allele in gnomAD v4.1 (AF=6.27e-07), which ENIGMA deems not informative for an outbred population.
No pathogenic criteria beyond PM2_Supporting were met. PVS1, PS1, PS3, PS4, PP1, PP3, and PP4 are all not met or not applicable for this missense variant.
In silico predictions are consistent with a benign interpretation: BayesDel no-AF score -0.472575 and REVEL 0.228 are below pathogenic thresholds. The variant is not in a functional domain, not at a hotspot, and was not identified in any calibrated functional assay (ENIGMA Table 9).
ClinVar reports this variant as Uncertain Significance (4 submitters) and Likely Benign (1 submitter), with no expert panel classification (ClinVar VariationID: 433760).
No criteria match.
Met · 2
PM2 SupportingThe variant is absent from gnomAD v2.1 (non-cancer, exome). In gnomAD v4.1, it is observed as a single allele (AF=6.27e-07, 1/1,595,636) in the European (non-Finnish) population. Per ENIGMA guidance, a single observation in a gnomAD outbred population is not informative and does not preclude PM2_Supporting. The variant is also absent from gnomAD-Canada. Details ▾Hide ▴
Evidence considered
- Absent from gnomAD v2.1 (non-cancer
- exome only).
- Single allele in gnomAD v4.1 (AF=6.27e-07
- 1/1
- 595
- 636
- NFE AF=8.51e-07
- 175
- 494)
- deemed not informative per ENIGMA guidance.
- Absent from gnomAD-Canada v1.0.
Still missing
- Read depth at variant region not verified (ENIGMA requires ≥25x average depth).
Sources
BP1 StrongENIGMA BP1_Strong applies to missense variants outside a (potentially) clinically important functional domain with no predicted splicing impact (SpliceAI ≤ 0.1). This missense variant (p.Ile501Val) is at amino acid position 501, which is outside both BRCA2 clinically important functional domains (PALB2 binding: aa 10-40; DNA binding: aa 2481-3186). SpliceAI max delta is 0.0, indicating no splicing impact. BRCA2 exons 10 and 11 (codons 266-2281) contain 0 P/LP missense variants among 2,177 submitted to ClinVar, consistent with this region being a validated coldspot. Details ▾Hide ▴
Evidence considered
- Missense variant at position 501
- outside PALB2 binding domain (aa 10-40) and DNA binding domain (aa 2481-3186).
- SpliceAI max delta 0.0 — no splicing impact.
- BRCA2 exons 10/11 coldspot: 0/2
- 177 P/LP missense variants in ClinVar (Dines et al. 2020
- PMID:31911673).
Sources
Not met · 14 · evaluated, threshold not reached
PS1 No previously classified pathogenic or likely pathogenic variant with the same amino acid change (p.Ile501Val) was identified. SpliceAI predicts no splicing impact (max delta 0.0), excluding the splicing-based PS1 pathway. Details ▾Hide ▴
Evidence considered
- No P/LP comparator variant at residue 501 identified
- SpliceAI max delta 0.0.
Sources
PS3 This variant was not identified in the ENIGMA Specifications Table 9 curated functional assay results. No variant-specific functional studies demonstrating a damaging effect on protein function were found in the literature. Details ▾Hide ▴
PS4 No case-control study demonstrating significantly increased prevalence in affected individuals was identified. The variant is not present in the ENIGMA Supplementary Table 7 reference set and lacks case-control OR data. Details ▾Hide ▴
Evidence considered
- Not present in ENIGMA ST7 posterior probability table
- no case-control data available.
Still missing
- No case-control or enrichment data for this variant.
Sources
cspec ↗vcep_supplementarytables_v1_2_2024_11_18
PP1 No co-segregation data or quantitative likelihood ratio analysis is available for this variant. ENIGMA requires LR ≥ 2.08 for PP1_Supporting from a quantitative co-segregation method. Details ▾Hide ▴
Evidence considered
- No co-segregation or pedigree LR data available for this variant.
Still missing
- No family segregation studies identified.
Sources
PP3 ENIGMA PP3 requires either (a) a missense variant inside a clinically important functional domain with BayesDel no-AF ≥ 0.30, or (b) SpliceAI ≥ 0.2. The variant is at position 501, outside both clinically important functional domains (PALB2 binding: aa 10-40; DNA binding: aa 2481-3186). BayesDel no-AF score is -0.472575 (< 0.30). SpliceAI max delta is 0.0 (< 0.2). Neither condition is satisfied. Details ▾Hide ▴
Evidence considered
- Position 501 outside clinically important functional domains.
- BayesDel no-AF score -0.472575 (< 0.30 threshold).
- SpliceAI max delta 0.0 (< 0.2 threshold).
- REVEL score 0.228.
Sources
PP4 ENIGMA PP4 requires a combined likelihood ratio from multifactorial clinical data (LR ≥ 2.08 for Supporting). The variant was not found in the Li et al. 2020 clinical-history LR table (PMID:31853058), the Parsons et al. 2019 multifactorial analysis (HUMU-40-1557-s001), or the ENIGMA ST7 reference set. No clinical-history or multifactorial LR data are available. Details ▾Hide ▴
Evidence considered
- Not present in Li et al. 2020 clinical-history LR table.
- Not present in Parsons et al. 2019 multifactorial likelihood data (HUMU-40-1557-s001).
- Not present in ENIGMA ST7 posterior probability table.
Still missing
- No clinical-history or multifactorial likelihood data available.
Sources
cspec ↗vcep_pmid_31853058_brca2_clinical_history_lrvcep_humu_40_1557_s001vcep_supplementarytables_v1_2_2024_11_18
BA1 ENIGMA BA1 requires FAF > 0.1% (0.001) in gnomAD non-founder populations. The variant has an allele frequency of 8.51e-07 (0.000085%) in the European (non-Finnish) population in gnomAD v4.1 and is absent from gnomAD v2.1. This is far below the BA1 threshold. Details ▾Hide ▴
Evidence considered
- Absent from gnomAD v2.1.
- gnomAD v4.1 AF = 8.51e-07 (NFE)
- far below BA1 threshold of 0.001.
Sources
BS1 ENIGMA BS1_Supporting requires FAF > 0.002% (0.00002) and BS1_Strong requires FAF > 0.01% (0.0001). The highest observed AF is 8.51e-07 in gnomAD v4.1 NFE, far below the BS1_Supporting threshold of 0.00002. FAF values are not available from gnomAD for this variant. Details ▾Hide ▴
Evidence considered
- Absent from gnomAD v2.1.
- gnomAD v4.1 NFE AF = 8.51e-07
- below BS1_Supporting threshold of 2e-05.
Still missing
- FAF (filter allele frequency) not available from gnomAD for this variant.
Sources
BS2 ENIGMA BS2 requires co-occurrence of the variant in trans with a known P/LP variant in the same gene, with absence of Fanconi Anemia phenotype, scored per Specifications Table 8. No such co-occurrence data are available for this variant. Details ▾Hide ▴
Evidence considered
- No co-occurrence/trans data with Fanconi Anemia phenotype assessment available.
Still missing
- No trans co-occurrence data identified.
Sources
BS3 The variant was not identified in the ENIGMA Specifications Table 9 curated functional assay results assigning BS3 codes. No well-established functional studies demonstrating no damaging effect on protein function were found in the literature. Details ▾Hide ▴
BS4 ENIGMA BS4 requires lack of segregation in affected family members as measured by quantitative co-segregation analysis (LR ≤ 0.48 for Supporting). No segregation data are available for this variant. The variant is not present in the ENIGMA ST7 reference set or the Parsons et al. 2019 multifactorial analysis. Details ▾Hide ▴
Evidence considered
- No segregation or cosegregation LR data available
- not in ST7 or Parsons et al. 2019.
Still missing
- No family segregation data.
Sources
BP4 ENIGMA BP4_Supporting applies to missense variants inside a clinically important functional domain with BayesDel no-AF ≤ 0.18 and SpliceAI ≤ 0.1. Position 501 is outside both clinically important functional domains. For missense variants outside domains, the bioinformatic evidence is captured by BP1_Strong rather than BP4. Details ▾Hide ▴
Evidence considered
- Position 501 outside clinically important functional domains — BP4 domain requirement not met.
- BayesDel no-AF -0.472575 and SpliceAI 0.0 would satisfy BP4 thresholds if inside a domain.
Sources
BP5 ENIGMA BP5 requires a combined likelihood ratio against pathogenicity from multifactorial clinical data (LR ≤ 0.48 for Supporting). The variant was not found in the Li et al. 2020 clinical-history LR table, the Parsons et al. 2019 multifactorial analysis, or the ENIGMA ST7 reference set. No clinical-history or multifactorial LR data are available. Details ▾Hide ▴
Evidence considered
- Not present in Li et al. 2020 clinical-history LR table.
- Not present in Parsons et al. 2019 multifactorial likelihood data.
- Not present in ENIGMA ST7 posterior probability table.
Still missing
- No clinical-history or multifactorial LR data available.
Sources
cspec ↗vcep_pmid_31853058_brca2_clinical_history_lrvcep_humu_40_1557_s001vcep_supplementarytables_v1_2_2024_11_18
BP7 ENIGMA BP7_Strong (RNA) requires well-established mRNA functional studies showing no damaging effect. No such data are available. ENIGMA BP7_Supporting applies to silent variants inside domains (if BP4 met) or intronic variants beyond +7/-21 (if BP4 met). This missense variant does not qualify for either BP7 pathway. Details ▾Hide ▴
Evidence considered
- Missense variant
- no mRNA functional studies available. BP7_Supporting pathways require silent or intronic variant type.
Still missing
- No mRNA transcript or splicing assay data.
Sources
Not applicable · 10· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/APVS1 is defined for null variants (nonsense, frameshift, canonical ±1,2 splice sites, initiation codon, exon deletions) per ENIGMA BRCA2 specifications. NM_000059.4:c.1501A>G is a missense variant (p.Ile501Val) and does not qualify. Details ▾Hide ▴
Evidence considered
- Missense substitution
- ENIGMA PVS1 rules apply only to null variant types.
Sources
PS2 VCEPPS2 is marked Not Applicable by the ENIGMA BRCA2 VCEP specifications. Details ▾Hide ▴
PM1 VCEPPM1 is captured as a component of bioinformatic analysis under PP3/BP4 per ENIGMA BRCA2 VCEP specifications. The variant resides at amino acid position 501, which is outside both clinically important functional domains (BRCA2 PALB2 binding domain aa 10-40; BRCA2 DNA binding domain aa 2481-3186). Details ▾Hide ▴
Evidence considered
- Position 501 is outside ENIGMA-defined clinically important functional domains
- PM1 component integrated into PP3/BP4 assessment.
Sources
PM5 N/AENIGMA BRCA2 VCEP repurposes PM5 exclusively for protein termination codon (PTC) variants in exons where a different proven pathogenic PTC has been observed. NM_000059.4:c.1501A>G is a missense variant (p.Ile501Val), not a PTC. Details ▾Hide ▴
Evidence considered
- Missense variant
- ENIGMA PM5 applies only to PTC variants.
Sources
cspec ↗vcep_specifications_table4_v1_2_2024_11_18
PM6 VCEPPM6 is marked Not Applicable by the ENIGMA BRCA2 VCEP specifications. Details ▾Hide ▴
PP2 VCEPPP2 is marked Not Applicable by the ENIGMA BRCA2 VCEP specifications. Details ▾Hide ▴
PP5 VCEPPP5 is Not Applicable per ENIGMA BRCA2 VCEP specifications. This criterion is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Details ▾Hide ▴
BP2 VCEPBP2 is marked Not Applicable by the ENIGMA BRCA2 VCEP specifications. Details ▾Hide ▴
BP6 VCEPBP6 is marked Not Applicable by the ENIGMA BRCA2 VCEP specifications. Details ▾Hide ▴
PS5 N/APS5 is not a defined criterion in the ACMG/AMP framework. PP5 is Not Applicable per ENIGMA BRCA2 VCEP specifications (not for use as recommended by the ClinGen SVI VCEP Review Committee). Details ▾Hide ▴
Evidence considered
- Not a standard ACMG/AMP criterion
- PP5 is not in use per ENIGMA BRCA2 VCEP.
Sources
Identifiers
- Gene
- BRCA2
- Transcript
- NM_000059.4
- Coding (HGVS c.)
- NM_000059.4:c.1501A>G
- Protein (HGVS p.)
- NP_000050.3:p.(Ile501Val)
- GRCh38
- chr13:32332979 A>G
- GRCh37
- chr13:32907116 A>G
- ClinVar
- 433760
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
1 / 1,595,636 alleles
AF 6.27e-07 · 0 homozygotes
gnomAD v2.1
Allele count data not recorded
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 6.3e-07 · 1 / 1,595,636 alleles · 0 hom
| European (non-Finnish)1 / 1,175,494 | 8.5e-07 |
0 alternate alleles recorded in 9 other groups: Remaining individuals, Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish, African/African American.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 6.26709e-07; MAF= 0.00006%, 1/1595636 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 8.50706e-07; MAF= 0.00009%, 1/1175494 alleles, homozygotes = 0).
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.228
- BayesDel
- -0.473
How the predictions were used
PP3 ENIGMA PP3 requires either (a) a missense variant inside a clinically important functional domain with BayesDel no-AF ≥ 0.30, or (b) SpliceAI ≥ 0.2. The variant is at position 501, outside both clinically important functional domains (PALB2 binding: aa 10-40; DNA binding: aa 2481-3186). BayesDel no-AF score is -0.472575 (< 0.30). SpliceAI max delta is 0.0 (< 0.2). Neither condition is satisfied. Details ▾Hide ▴
Evidence considered
- Position 501 outside clinically important functional domains.
- BayesDel no-AF score -0.472575 (< 0.30 threshold).
- SpliceAI max delta 0.0 (< 0.2 threshold).
- REVEL score 0.228.
Sources
BP4 ENIGMA BP4_Supporting applies to missense variants inside a clinically important functional domain with BayesDel no-AF ≤ 0.18 and SpliceAI ≤ 0.1. Position 501 is outside both clinically important functional domains. For missense variants outside domains, the bioinformatic evidence is captured by BP1_Strong rather than BP4. Details ▾Hide ▴
Evidence considered
- Position 501 outside clinically important functional domains — BP4 domain requirement not met.
- BayesDel no-AF -0.472575 and SpliceAI 0.0 would satisfy BP4 thresholds if inside a domain.
Sources
BP7 ENIGMA BP7_Strong (RNA) requires well-established mRNA functional studies showing no damaging effect. No such data are available. ENIGMA BP7_Supporting applies to silent variants inside domains (if BP4 met) or intronic variants beyond +7/-21 (if BP4 met). This missense variant does not qualify for either BP7 pathway. Details ▾Hide ▴
Evidence considered
- Missense variant
- no mRNA functional studies available. BP7_Supporting pathways require silent or intronic variant type.
Still missing
- No mRNA transcript or splicing assay data.
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.228. BayesDel score = -0.472575.
7 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 coldspot regions. In BRCA2 exons 10 and 11 (codons 266-2281), 0 of 2,177 missense variants were classified as pathogenic or likely pathogenic, establishing this region as a coldspot. Proposed that missense variants in coldspots can be classified as likely benign using Bayesian odds ratio thresholds.→ BP1 Does not name this variant
Source detail
Exon 10 and 11 ... 0 (0) ... 110 (5.1) ... 2067 (94.9) ... 2177 (100.0)
Location Table 1; Results, BRCA2 section
Other recorded publications
-
PMID 26467025 ↗A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.Describes a standardized rules-based DNA variant scoring system for pathogenicity assessment in Mendelian disorders. Analyzed over 16,500 pathogenicity assessments on 11,894 variants from 338 genes. General methodology paper; no BRCA2-specific or variant-specific data.Does not name this variant
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PMID 12692171 ↗American Society of Clinical Oncology policy statement update: genetic testing for cancer susceptibility.American Society of Clinical Oncology · 2003American Society of Clinical Oncology policy statement update on genetic testing for cancer susceptibility. Outlines general principles for integrating cancer predisposition testing into oncology practice. No variant-specific data.Does not name this variant
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PMID 20065170 ↗American Society of Clinical Oncology policy statement update: genetic and genomic testing for cancer susceptibility.Robson ME et al. · 2010American Society of Clinical Oncology policy statement update on genetic and genomic testing for cancer susceptibility. Provides general guidance on responsible integration of genetic testing into clinical oncology. No variant-specific data.Does not name this variant
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PMID 20301425 ↗BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer.Adam MP et al. · 1993GeneReviews entry for BRCA1- and BRCA2-associated hereditary breast and ovarian cancer. Comprehensive overview of clinical characteristics, genetic counseling, and management. No individual variant assessment data.Does not name this variant
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PMID 23188549 ↗NSGC practice guideline: risk assessment and genetic counseling for hereditary breast and ovarian cancer.NSGC practice guideline for risk assessment and genetic counseling for hereditary breast and ovarian cancer. Provides recommendations for BRCA1/2 genetic testing referral, pedigree assessment, and medical management. Does not discuss individual variants or classification evidence.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. Defines minimum adequate family history elements and provides guidance on interpreting family history for hereditary cancer risk assessment. No individual variant data.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
1 / 1,595,636 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
4 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/433760/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/13-32907116-A-G?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr13-32332979-A-G?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/13-32332979-A-G
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000059.4%3Ac.1501…
- OncoKB ↗www.oncokb.org/gene/BRCA2/I501V
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=BRCA2+c.1501A%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= 6.26709e-07; MAF= 0.00006%, 1/1595636 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 8.50706e-07; MAF= 0.00009%, 1/1175494 alleles, homozygotes = 0).
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Uncertain significance (4 clinical laboratories) and as Likely benign (1 clinical laboratory). (ClinVarID = 433760)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.228. BayesDel score = -0.472575.
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.