About BRCA2
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
BRCA2 c.8183T>C, p.(Val2728Ala)
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: 2
Pathogenic criteria applied · 0
No pathogenic criterion marked as applied in the recorded assessment.
Benign criteria applied · 2
BS3Strong
BS3 · strong
ENIGMA Specifications Table 9 assigns BS3_Strong for c.8183T>C p.(Val2728Ala) based on a calibrated functional study (Richardson et al. 2021, PMID:33609447) demonstrating that this variant exhibits protein function similar to benign control variants in a homology-directed repair (HDR) assay.
BP4Supporting
BP4 · supporting
ENIGMA BP4_Supporting applies to missense variants inside a clinically important functional domain with no predicted impact via protein change or splicing: BayesDel no-AF score ≤0.18 AND SpliceAI ≤0.1. This variant satisfies both conditions (BayesDel=0.103, SpliceAI max delta=0.01) and is located within the BRCA2 DNA binding domain (aa 2481-3186).
Recorded classification: Likely benign
ENIGMA BRCA1/BRCA2 v1.2.0 Table 3 classification framework was used as the primary authority. The variant has 1 met Strong Benign criterion (BS3_Strong: calibrated functional assay shows HDR activity similar to benign controls, PMID:33609447) and 1 met Supporting Benign criterion (BP4_Supporting: BayesDel no-AF=0.103 ≤0.18, SpliceAI max delta=0.01 ≤0.1, inside DNA binding domain). No pathogenic criteria are met. The combination of 1 Strong (Benign) + 1 Supporting (Benign) satisfies the ENIGMA Table 3 Likely Benign rule. No conflicting evidence to resolve via the point system.
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
4 / 1,614,072 alleles
gnomAD v4.1: 4 / 1,614,072 alleles. Recorded AF 2.4782e-06. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 3.18471e-05; MAF= 0.00318%, 1/31400 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000114811; MAF= 0.01148%, 1/8710 alleles, homozygotes = 0).
No listed criterion applied
SpliceAI score
0.010 maximum delta
Recorded SpliceAI maximum delta score: 0.010. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
9 reported laboratory submissions
7 Uncertain significance · 1 Uncertain Significance · 1 Likely benign.
Context only
ClinVar ↗
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
1 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV105932213, n = 1 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.
29 criteria with recorded statuses: 2 met · 13 not met · 0 not assessed · 14 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_000059.4:c.8183T>C (p.Val2728Ala) is a missense variant in exon 18 of BRCA2, located within the DNA binding domain (aa 2481-3186).
This variant is present at extremely low frequency in population databases: gnomAD v2.1 (1/31,400 alleles, exclusively in genomes; exome not covered) and gnomAD v4.1 (4/1,614,072 alleles, grpmax FAF=1.746e-05). It is absent from gnomAD-Canada v1.0.
In ClinVar (Variation ID 141399), this variant is classified as Uncertain Significance by seven clinical laboratories and Likely Benign by one laboratory (criteria provided, single submitter).
ENIGMA Specifications Table 9 assigns BS3_Strong based on a calibrated functional study (Richardson et al. 2021, PMID:33609447) demonstrating that V2728A exhibits HDR activity similar to benign control variants.
ENIGMA BP4_Supporting is met: the variant is inside the DNA binding domain with no predicted impact via protein change (BayesDel no-AF=0.103, ≤0.18) and no predicted splicing impact (SpliceAI max delta=0.01, ≤0.1).
The clinical-history likelihood ratio from Li et al. 2020 (PMID:31853058) is LR=1.24 based on 1 proband, falling in the neutral zone and providing no evidence for PP4 or BP5.
No pathogenic comparator exists at residue Val2728 (c.8182G>A p.Val2728Ile is classified as benign by ENIGMA), so PS1 is not met. PVS1, PM5, and other null-variant criteria are not applicable to this missense substitution.
Applying ENIGMA Table 3 combination rules: BS3_Strong (1 Strong Benign) + BP4_Supporting (1 Supporting Benign) meets the likely benign rule [1 Strong (Benign) + 1 Supporting (Benign)]. The total benign evidence is one Strong and one Supporting criterion with no pathogenic criteria met.
No criteria match.
Met · 2
BS3 StrongENIGMA Specifications Table 9 assigns BS3_Strong for c.8183T>C p.(Val2728Ala) based on a calibrated functional study (Richardson et al. 2021, PMID:33609447) demonstrating that this variant exhibits protein function similar to benign control variants in a homology-directed repair (HDR) assay. Details ▾Hide ▴
Evidence considered
- ENIGMA Table 9 BS3_Strong assignment: 'Reported by one calibrated study to exhibit protein function similar to benign control variants (PMID:33609447) (BS3 met).'
Still missing
- Single calibrated study
- replication in an independent functional assay would further strengthen the evidence.
Sources
BP4 SupportingENIGMA BP4_Supporting applies to missense variants inside a clinically important functional domain with no predicted impact via protein change or splicing: BayesDel no-AF score ≤0.18 AND SpliceAI ≤0.1. This variant satisfies both conditions (BayesDel=0.103, SpliceAI max delta=0.01) and is located within the BRCA2 DNA binding domain (aa 2481-3186). Details ▾Hide ▴
Evidence considered
- BayesDel no-AF=0.103 (≤0.18)
- SpliceAI max delta=0.01 (≤0.1)
- residue 2728 is inside BRCA2 DNA binding domain (aa 2481-3186).
Sources
Not met · 13 · evaluated, threshold not reached
PS1 No previously classified pathogenic missense variant exists at the same amino acid residue (Val2728). The comparator c.8182G>A p.(Val2728Ile) is classified as benign (IARC Class 1) by the ENIGMA multifactorial analysis (Parsons et al. 2019, PMID:31131967) and assigned no PS3/BS3 code by ENIGMA Table 9. Details ▾Hide ▴
Evidence considered
- Same-residue variant c.8182G>A p.(Val2728Ile) is benign per HUMU SuppT1 (IARC Class 1
- posterior probability 0.000345)
- ENIGMA Table 9 assigns it no functional code.
Sources
vcep_humu_40_1557_s001vcep_specifications_table9_v1_2_2024_11_1831131967
PS3 ENIGMA Specifications Table 9 assigns BS3 (not PS3) for this variant based on calibrated functional assay data showing protein function similar to benign control variants (PMID:33609447). The functional evidence points toward benign effect, not pathogenic. Details ▾Hide ▴
Evidence considered
- ENIGMA Table 9: c.8183T>C p.(Val2728Ala) assigned BS3_Strong
- not PS3
- Richardson 2021 (PMID:33609447) reports neutral function.
Sources
vcep_specifications_table9_v1_2_2024_11_1833609447
PS4 No case-control study demonstrates significantly increased prevalence of this variant in affected individuals versus controls. The variant is absent from the ENIGMA ST7 Reference Set and no published PS4-level evidence was identified. Details ▾Hide ▴
Evidence considered
- Variant not present in ENIGMA ST7 Reference Set
- no case-control study with p≤0.05 and OR≥4 identified
- ClinVar submissions lack proband counts for PS4-level analysis.
Still missing
- No published case-control study counting unrelated affected individuals with this variant.
Sources
vcep_supplementarytables_v1_2_2024_11_18
PM2 ENIGMA PM2_Supporting requires absence from both gnomAD v2.1 non-cancer exome and v3.1 non-cancer. The variant is present in gnomAD v2.1 genomes (1/31,400 alleles, AF=3.18e-05) and in gnomAD v4.1 (4/1,614,072 alleles, AF=2.48e-06). It is not absent from population controls. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: 1 allele in 31
- 400 (genome only
- exome not covered)
- gnomAD v4.1: 4 alleles in 1
- 614
- 072
- gnomAD-Canada: absent.
Sources
PP1 No cosegregation data available for this variant. No published studies demonstrate variant tracking with disease in multiple affected family members, and no quantitative cosegregation LR has been calculated. Details ▾Hide ▴
Evidence considered
- Exploratory search found no cosegregation evidence
- variant not assessed in any published segregation analysis.
Still missing
- No family-based cosegregation data identified.
PP3 ENIGMA PP3 requires BayesDel no-AF score ≥0.30 for missense variants inside a clinically important functional domain (or SpliceAI ≥0.2 for predicted splicing). The variant has BayesDel=0.103 and SpliceAI max delta=0.01, both below PP3 thresholds. Details ▾Hide ▴
Evidence considered
- BayesDel no-AF=0.103 (<0.30 threshold)
- SpliceAI max delta=0.01 (<0.20 threshold)
- REVEL=0.614
- residue 2728 is inside BRCA2 DNA binding domain (aa 2481-3186).
Sources
PP4 The clinical-history likelihood ratio from Li et al. 2020 (PMID:31853058) is LR=1.24 (1 proband), which falls in the neutral zone (>0.48 and <2.08). Per ENIGMA specification, this LR does not provide supporting evidence in either direction. Details ▾Hide ▴
Evidence considered
- Li et al. 2020 clinical-history LR=1.24 (N_Probands=1)
- neutral zone per ENIGMA thresholds (Supporting requires LR≥2.08).
Sources
BA1 ENIGMA BA1 requires FAF >0.1% (0.001) in gnomAD non-founder populations. The variant has maximum allele frequency of 0.0115% in gnomAD v2.1 African/African American (1/8,710) and grpmax FAF of 1.746e-05 in v4.1, both far below the BA1 threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 max AF=0.0115% (African/African American
- 1/8
- 710)
- gnomAD v4.1 grpmax FAF=1.746e-05 (0.00175%)
- both well below 0.1% BA1 threshold.
Sources
BS1 ENIGMA BS1 requires FAF >0.002% in gnomAD v2.1 non-cancer exome or v3.1 non-cancer. The variant is absent from v2.1 exome (not covered, ac=0/an=0), and gnomAD v4.1 grpmax FAF=1.746e-05 (0.00175%) is below the BS1_Supporting threshold of 0.002%. BS1 thresholds are not met. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 exome: not covered (ac=0
- an=0)
- gnomAD v4.1 grpmax FAF=1.746e-05 (<0.00002 BS1_Supporting threshold)
- v4.1 raw AF=2.48e-06.
Still missing
- gnomAD v2.1 FAF unavailable for genome-only variant
- v3.1 FAF would be informative but v4.1 grpmax FAF is below BS1 thresholds.
Sources
BS2 No evidence of this variant observed in a homozygous state in individuals without Fanconi Anemia phenotype. Per ENIGMA Table 8, BS2 requires point assignment based on proband observations; no such data are available. Details ▾Hide ▴
Evidence considered
- No homozygous observations in gnomAD
- no published reports of biallelic BRCA2 c.8183T>C without FA phenotype.
Still missing
- No proband-level data for BS2 point assignment per ENIGMA Table 8.
BS4 No quantitative lack-of-segregation evidence is available. The variant is absent from the ENIGMA ST7 Reference Set and no published studies report non-segregation in affected family members. Details ▾Hide ▴
Evidence considered
- Variant not present in ENIGMA ST7 Reference Set
- no published segregation/non-segregation analysis identified.
Still missing
- No family-based segregation data for BS4 assessment.
Sources
vcep_supplementarytables_v1_2_2024_11_18
BP5 The clinical-history likelihood ratio from Li et al. 2020 (PMID:31853058) is LR=1.24 (1 proband), which falls in the neutral zone (>0.48 and <2.08). Per ENIGMA specification, this LR does not support BP5 (which requires LR≤0.48 for Supporting). Details ▾Hide ▴
Evidence considered
- Li et al. 2020 clinical-history LR=1.24 (N_Probands=1)
- neutral zone per ENIGMA thresholds (BP5_Supporting requires LR≤0.48).
Sources
PS5 No reputable source has recently reported this variant as pathogenic with unavailable supporting evidence. The variant is classified as VUS in ClinVar and as Likely Neutral by OncoKB. Details ▾Hide ▴
Not applicable · 14· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/APVS1 is applicable only to null variants (nonsense, frameshift, canonical splice ±1,2) per ENIGMA BRCA2 specification v1.2. NM_000059.4:c.8183T>C is a missense variant (p.Val2728Ala) and does not qualify. Details ▾Hide ▴
Evidence considered
- Missense substitution at c.8183
- not a null variant
- no evidence of nonsense-mediated decay or complete loss of function.
Sources
pvs1_variant_assessmentpvs1_gene_context
PS2 VCEPNot applicable per ENIGMA BRCA2 specification v1.2. Details ▾Hide ▴
Sources
PM1 VCEPNot applicable per ENIGMA BRCA2 specification v1.2. Details ▾Hide ▴
Sources
PM3 N/ANot applicable. PM3 requires detection in trans with a pathogenic variant for recessive disorders; no such observations exist for this variant and Fanconi Anemia. Details ▾Hide ▴
Sources
PM4 VCEPNot applicable per ENIGMA BRCA2 specification v1.2. PM4 applies to protein-length changes (in-frame deletions/insertions, stop-loss); this is a missense substitution. Details ▾Hide ▴
Sources
PM5 N/AENIGMA repurposes PM5 for protein termination codon (PTC) variants in exons where a different proven pathogenic PTC has been seen. This is a missense variant and does not qualify for PM5_PTC. Classic same-residue missense PM5 is not used in the ENIGMA BRCA2 framework. Details ▾Hide ▴
Evidence considered
- Missense variant
- PM5 is reserved for PTC variants per ENIGMA v1.2
- pm5_candidates.json confirms not_applicable.
Sources
pm5_candidatesvcep_specifications_table4_v1_2_2024_11_18
PM6 VCEPNot applicable per ENIGMA BRCA2 specification v1.2. Details ▾Hide ▴
Sources
PP2 VCEPNot applicable per ENIGMA BRCA2 specification v1.2. Details ▾Hide ▴
Sources
PP5 VCEPNot applicable per ENIGMA BRCA2 specification v1.2. Details ▾Hide ▴
Sources
BP1 N/AENIGMA BP1_Strong applies to missense variants located OUTSIDE a clinically important functional domain. Residue 2728 is within the BRCA2 DNA binding domain (aa 2481-3186), a clinically important functional domain per ENIGMA specification. BP1 is not applicable. Details ▾Hide ▴
Evidence considered
- Residue Val2728 is inside BRCA2 DNA binding domain (aa 2481-3186)
- BP1 requires location outside functional domain.
Sources
BP2 VCEPNot applicable per ENIGMA BRCA2 specification v1.2. Details ▾Hide ▴
Sources
BP3 VCEPNot applicable per ENIGMA BRCA2 specification v1.2. BP3 applies to in-frame deletions/insertions in repetitive regions; this is a missense substitution. Details ▾Hide ▴
Sources
BP6 VCEPNot applicable per ENIGMA BRCA2 specification v1.2. Details ▾Hide ▴
Sources
BP7 N/AENIGMA BP7_Supporting applies only to silent variants inside a functional domain (if BP4 met) or intronic variants outside conserved splice motifs. BP7_Strong (RNA) requires mRNA assay evidence showing no damaging effect on splicing. This is a missense variant inside the DNA binding domain with no mRNA assay data available; BP7 is not applicable. Details ▾Hide ▴
Evidence considered
- Missense variant inside functional domain
- BP7_Supporting is for silent/intronic variants only
- BP7_Strong(RNA) requires mRNA assay data
- which is not available.
Sources
Identifiers
- Gene
- BRCA2
- Transcript
- NM_000059.4
- Coding (HGVS c.)
- NM_000059.4:c.8183T>C
- Protein (HGVS p.)
- NP_000050.3:p.(Val2728Ala)
- GRCh38
- chr13:32363385 T>C
- GRCh37
- chr13:32937522 T>C
- ClinVar
- 141399
- COSMIC
- COSV105932213
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
4 / 1,614,072 alleles
AF 2.48e-06 · 0 homozygotes · FAF 1.75e-05
gnomAD v2.1
1 / 31,400 alleles
AF 3.18e-05 · 0 homozygotes
gnomAD-Canada v1.0
0 / 0 alleles
AF 0 · 0 homozygotes · FAF 0
By genetic ancestry
gnomAD v4.1
AF 2.5e-06 · 4 / 1,614,072 alleles · 0 hom · FAF 1.7e-05
| African/African American4 / 74,924 | 5.3e-05 |
0 alternate alleles recorded in 9 other groups: Remaining individuals, Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish, European (non-Finnish).
gnomAD v2.1
AF 3.2e-05 · 1 / 31,400 alleles · 0 hom
| African/African American1 / 8,710 | 0.00011 |
0 alternate alleles recorded in 7 other groups: Admixed American, Ashkenazi Jewish, East Asian, European (Finnish), European (non-Finnish), Remaining individuals, South Asian.
gnomAD-Canada
AF 0 · 0 / 0 alleles · 0 hom
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 2.4782e-06; MAF= 0.00025%, 4/1614072 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 5.33874e-05; MAF= 0.00534%, 4/74924 alleles, homozygotes = 0); grpmax FAF= 1.746e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 3.18471e-05; MAF= 0.00318%, 1/31400 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000114811; MAF= 0.01148%, 1/8710 alleles, homozygotes = 0).
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.614
- BayesDel
- 0.103
How the predictions were used
BP4 SupportingENIGMA BP4_Supporting applies to missense variants inside a clinically important functional domain with no predicted impact via protein change or splicing: BayesDel no-AF score ≤0.18 AND SpliceAI ≤0.1. This variant satisfies both conditions (BayesDel=0.103, SpliceAI max delta=0.01) and is located within the BRCA2 DNA binding domain (aa 2481-3186). Details ▾Hide ▴
Evidence considered
- BayesDel no-AF=0.103 (≤0.18)
- SpliceAI max delta=0.01 (≤0.1)
- residue 2728 is inside BRCA2 DNA binding domain (aa 2481-3186).
Sources
PP3 ENIGMA PP3 requires BayesDel no-AF score ≥0.30 for missense variants inside a clinically important functional domain (or SpliceAI ≥0.2 for predicted splicing). The variant has BayesDel=0.103 and SpliceAI max delta=0.01, both below PP3 thresholds. Details ▾Hide ▴
Evidence considered
- BayesDel no-AF=0.103 (<0.30 threshold)
- SpliceAI max delta=0.01 (<0.20 threshold)
- REVEL=0.614
- residue 2728 is inside BRCA2 DNA binding domain (aa 2481-3186).
Sources
BP7 N/AENIGMA BP7_Supporting applies only to silent variants inside a functional domain (if BP4 met) or intronic variants outside conserved splice motifs. BP7_Strong (RNA) requires mRNA assay evidence showing no damaging effect on splicing. This is a missense variant inside the DNA binding domain with no mRNA assay data available; BP7 is not applicable. Details ▾Hide ▴
Evidence considered
- Missense variant inside functional domain
- BP7_Supporting is for silent/intronic variants only
- BP7_Strong(RNA) requires mRNA assay data
- which is not available.
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01). REVEL score = 0.614. BayesDel score = 0.103001.
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
-
PMID 35736817 ↗Classification of BRCA2 Variants of Uncertain Significance (VUS) Using an ACMG/AMP Model Incorporating a Homology-Directed Repair (HDR) Functional Assay.Hu C et al. · 2022No paper-specific finding is recorded.
-
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.No paper-specific finding is recorded.
-
PMID 26467025 ↗A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.No paper-specific finding is recorded.
-
PMID 31415627 ↗A research-based gene panel to investigate breast, ovarian and prostate cancer genetic risk.Bishop MR et al. · 2019No paper-specific finding is recorded.
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PMID 31853058 ↗Classification of variants of uncertain significance in BRCA1 and BRCA2 using personal and family history of cancer from individuals in a large hereditary cancer multigene panel testing cohort.Li H et al. · 2020No paper-specific finding is recorded.
-
PMID 32377563 ↗Prediction of the functional impact of missense variants in BRCA1 and BRCA2 with BRCA-ML.Hart SN et al. · 2020No paper-specific finding is recorded.
-
PMID 33609447 ↗Strong functional data for pathogenicity or neutrality classify BRCA2 DNA-binding-domain variants of uncertain significance.Richardson ME et al. · 2021No 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
4 / 1,614,072 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.010
Open source ↗
ClinVar
7 Uncertain significance · 1 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/141399/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/13-32937522-T-C?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr13-32363385-T-C?dataset=gn…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000059.4%3Ac.8183…
- OncoKB ↗www.oncokb.org/gene/BRCA2/V2728A
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=140307272
- 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= 2.4782e-06; MAF= 0.00025%, 4/1614072 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 5.33874e-05; MAF= 0.00534%, 4/74924 alleles, homozygotes = 0); grpmax FAF= 1.746e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 3.18471e-05; MAF= 0.00318%, 1/31400 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000114811; MAF= 0.01148%, 1/8710 alleles, homozygotes = 0).
ClinVar
This variant has been reported in ClinVar as Uncertain significance (7 clinical laboratories) and as Uncertain Significance (1 clinical laboratory) and as Likely benign (1 clinical laboratory). (ClinVarID = 141399)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01). REVEL score = 0.614. BayesDel score = 0.103001.
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; COSV105932213, n = 1 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.