About BRCA2
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
BRCA2 c.8242G>A, p.(Gly2748Ser)
Classification
Uncertain significance
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is uncertain. Select a step to read what it means.
Uncertain.The recorded classification is uncertain significance.
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: 2
Benign evidence criteria: 0
Pathogenic criteria applied · 2
PS3Strong
PS3 · strong
In the ENIGMA BRCA2 functional evidence table, this exact variant, c.8242G>A (p.Gly2748Ser), is assigned PS3 at strong strength based on one calibrated functional study reported to show a damaging effect consistent with pathogenic control variants.
PP3Supporting
PP3 · supporting
This missense variant lies within the BRCA2 DNA-binding domain, a clinically important functional region used by the ENIGMA bioinformatic framework. BayesDel no-AF is 0.454479, which is above the ENIGMA PP3 threshold of 0.30, SpliceAI shows no significant splice effect with a maximum delta score of 0.06, and REVEL is 0.842; together these findings support a damaging protein effect and meet PP3 at supporting strength.
Benign criteria applied · 0
No benign criterion marked as applied in the recorded assessment.
Recorded classification: Uncertain significance
ENIGMA BRCA1/BRCA2 Specification v1.2 final-classification framework (Table 3 criteria-combination rules; ACMG/AMP 2015 with ENIGMA adaptations).
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
6 / 1,614,064 alleles
gnomAD v4.1: 6 / 1,614,064 alleles. Recorded AF 3.71732e-06. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.20448e-05; MAF= 0.00120%, 3/249070 alleles, homozygotes = 0) and has highest observed frequency in the Admixed American population (AF= 5.78469e-05; MAF= 0.00578%, 2/34574 alleles, homozygotes = 0); grpmax FAF= 9.58e-06.
No listed criterion applied
SpliceAI score
0.060 maximum delta
Recorded SpliceAI maximum delta score: 0.060. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
9 reported laboratory submissions
7 Likely pathogenic · 1 Pathogenic · 1 likely pathogenic.
Context only
ClinVar ↗
Functional evidence
Statement recorded
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Loss-of-function; curated oncogenicity label: Likely Oncogenic.
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.
28 criteria with recorded statuses: 2 met · 7 not met · 8 not assessed · 11 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
The BRCA2 c.8242G>A (p.Gly2748Ser; G2748S) variant has been reported in ClinVar, where the current expert-panel overall classification is uncertain significance, while multiple clinical laboratory submissions classify it as likely pathogenic or pathogenic.
This variant is present at very low frequency in population databases, including gnomAD v2.1 at 3/249070 alleles (AF 1.20e-05; grpmax FAF 9.58e-06) and gnomAD v4.1 at 6/1614064 alleles (AF 3.72e-06), which is below ENIGMA BS1 and BA1 thresholds but means PM2 is not met because the variant is not absent from controls.
In the ENIGMA BRCA2 functional evidence table, this exact variant is assigned PS3 at strong strength based on one calibrated study reported to show a damaging functional effect consistent with pathogenic control variants.
This missense change lies within the BRCA2 DNA-binding domain; BayesDel no-AF is 0.454479, above the ENIGMA PP3 threshold of 0.30, SpliceAI predicts no significant splice effect with a maximum delta score of 0.06, and REVEL is 0.842, supporting a damaging protein effect without predicted splice disruption.
No criteria match.
Met · 2
PS3 StrongIn the ENIGMA BRCA2 functional evidence table, this exact variant, c.8242G>A (p.Gly2748Ser), is assigned PS3 at strong strength based on one calibrated functional study reported to show a damaging effect consistent with pathogenic control variants. Details ▾Hide ▴
Rule
Apply PS3 when calibrated functional studies support a damaging effect.
Evidence considered
- Specifications Table 9 lists BRCA2 c.8242G>A p.(Gly2748Ser) as PS3 Strong.
- Table 9 summary states one calibrated study showed a damaging functional effect.
Sources
vcep_specifications_table9_v1_2_2024_11_18PMID:33609447 ↗
PP3 SupportingThis missense variant lies within the BRCA2 DNA-binding domain, a clinically important functional region used by the ENIGMA bioinformatic framework. BayesDel no-AF is 0.454479, which is above the ENIGMA PP3 threshold of 0.30, SpliceAI shows no significant splice effect with a maximum delta score of 0.06, and REVEL is 0.842; together these findings support a damaging protein effect and meet PP3 at supporting strength. Details ▾Hide ▴
Rule
For BRCA2 missense variants inside a clinically important domain, apply PP3_Supporting when BayesDel no-AF >= 0.30; splicing prediction is considered separately.
Evidence considered
- Protein position 2748 lies within the BRCA2 DNA-binding domain aa 2481-3186.
- BayesDel no-AF 0.454479 >= 0.30.
- SpliceAI max delta 0.06.
- REVEL 0.842.
Sources
Not met · 7 · evaluated, threshold not reached
PVS1 This missense variant is not a nonsense, frameshift, canonical ±1/2 splice-site, initiation-codon, or deletion event, and no RNA-only evidence was identified to support a null-effect mechanism. Available evidence does not support applying PVS1 for this variant. Details ▾Hide ▴
Rule
ENIGMA/ClinGen PVS1 applies to null variants or qualifying RNA-only loss-of-function evidence.
Evidence considered
- BRCA2 is PVS1-eligible at the gene level in the ENIGMA framework.
- NM_000059.3:c.8242G>A is a missense change
- p.(Gly2748Ser)
- outside the default null-variant buckets.
Sources
PM2 This variant is not absent from population databases. It is present in gnomAD v2.1 at 3/249070 alleles (AF 1.20e-05) and in gnomAD v4.1 at 6/1614064 alleles (AF 3.72e-06), so the ENIGMA requirement for absence from controls is not met. Details ▾Hide ▴
Rule
ENIGMA PM2_Supporting requires absence from controls in gnomAD.
Evidence considered
- gnomAD v2.1 total AF 1.20448e-05
- 3 alleles.
- gnomAD v4.1 total AF 3.71732e-06
- 6 alleles.
Sources
BA1 The population data are well below the ENIGMA BA1 threshold. The gnomAD v2.1 group maximum filter allele frequency is 9.58e-06, which is below the BA1 cutoff of 0.001. Details ▾Hide ▴
Rule
BA1 requires a non-founder population FAF > 0.001.
Evidence considered
- gnomAD v2.1 grpmax FAF 9.58e-06.
Sources
BS1 The population frequency does not reach the ENIGMA BS1 thresholds. The gnomAD v2.1 group maximum filter allele frequency is 9.58e-06, which is below both the BS1 supporting threshold of 2.0e-05 and the BS1 strong threshold of 1.0e-04. Details ▾Hide ▴
Rule
BS1_Supporting requires FAF > 0.00002 and BS1_Strong requires FAF > 0.0001.
Evidence considered
- gnomAD v2.1 grpmax FAF 9.58e-06.
Sources
BS3 Available functional evidence does not support a benign effect. Instead, the ENIGMA BRCA2 functional evidence table assigns this exact variant PS3 at strong strength based on a calibrated damaging functional result, so BS3 is not met. Details ▾Hide ▴
Rule
BS3 requires calibrated functional studies showing no damaging effect.
Evidence considered
- Specifications Table 9 lists this variant as PS3 Strong rather than BS3.
Sources
vcep_specifications_table9_v1_2_2024_11_18PMID:33609447 ↗
BP1 This missense variant does not meet BP1 because it lies within the BRCA2 DNA-binding domain, which is a clinically important functional region in the ENIGMA framework. BP1 is reserved for missense, silent, or in-frame variants outside these regions with no predicted splice impact. Details ▾Hide ▴
Rule
BP1_Strong applies only outside clinically important domains with no splice effect predicted.
Evidence considered
- Protein position 2748 lies in the BRCA2 DNA-binding domain aa 2481-3186.
- SpliceAI max delta is 0.06
- but the domain requirement for BP1 is not met.
Sources
BP4 BP4 is not met. Although SpliceAI predicts no significant splice impact with a maximum delta score of 0.06, the variant is inside the BRCA2 DNA-binding domain and the BayesDel no-AF score is 0.454479, which is above the BP4 benign threshold of 0.18 and instead supports predicted protein impact. Details ▾Hide ▴
Rule
BP4 for BRCA2 missense variants in clinically important domains requires BayesDel no-AF <= 0.18 and SpliceAI <= 0.1.
Evidence considered
- BayesDel no-AF 0.454479 > 0.18.
- SpliceAI max delta 0.06 <= 0.1.
- REVEL 0.842.
Sources
Not assessed · 8 · no assessment recorded
PS1 No validated same-amino-acid pathogenic or likely pathogenic comparator was identified in the reviewed materials, so PS1 was not assessed from the currently available evidence. Details ▾Hide ▴
Rule
Use PS1 only when the same amino-acid change or same splice effect has already been established under the ENIGMA rules.
Evidence considered
- ENIGMA BRCA2 PS1 requires an established pathogenic or likely pathogenic comparator with the same protein or splice effect.
Still missing
- A directed same-amino-acid comparator review would be needed to assess PS1.
Sources
PS4 No case-control study or quantitative enrichment analysis for this exact variant was identified in the reviewed materials. Available evidence is insufficient to determine whether the prevalence in affected individuals is significantly increased over controls. Details ▾Hide ▴
Rule
PS4 requires significant enrichment in affected individuals compared with controls.
Evidence considered
- ClinVar shows the variant has been observed clinically
- but this does not establish PS4.
- No exact-variant case-control metric was recovered from the reviewed BRCA2 supporting tables.
Still missing
- No odds ratio or p-value for this exact variant was identified.
- The reviewed ENIGMA posterior probability and multifactorial tables did not provide a usable exact-variant PS4 determination.
Sources
PM3 No evidence was identified that this variant was observed in trans with another BRCA2 pathogenic or likely pathogenic variant in an individual with BRCA2-related Fanconi anemia. PM3 was therefore not assessed. Details ▾Hide ▴
Rule
Use PM3 only for qualifying BRCA2-related Fanconi anemia observations.
Evidence considered
- ENIGMA PM3 for BRCA2 is restricted to recessive Fanconi anemia presentations with defined scoring rules.
Still missing
- No phase-confirmed Fanconi anemia data were identified.
Sources
PP1 No quantitative co-segregation analysis or family-based likelihood ratio meeting ENIGMA thresholds was identified for this variant. PP1 was not assessed from the available evidence. Details ▾Hide ▴
Rule
PP1 requires quantitative cosegregation evidence reaching ENIGMA likelihood-ratio thresholds.
Evidence considered
- ClinVar citations include family-based literature
- but no usable quantitative PP1 likelihood ratio was recovered for this exact variant.
Still missing
- No segregation likelihood ratio was identified.
Sources
PP4 No exact-variant clinical-history likelihood ratio meeting ENIGMA PP4 thresholds was identified. The reviewed BRCA2 clinical-history likelihood-ratio table did not provide a usable entry for this variant, so PP4 was not assessed. Details ▾Hide ▴
Rule
PP4 in BRCA2 ENIGMA requires a qualifying multifactorial clinical likelihood ratio.
Evidence considered
- The BRCA2 Li 2020 clinical-history LR workbook was reviewed without a usable exact-variant match.
Still missing
- No exact-variant clinical-history LR was identified.
- No combined multifactorial LR qualifying for PP4 was recovered.
Sources
BS2 No qualifying observations in adults without BRCA2-related Fanconi anemia features were identified to score BS2 under the ENIGMA point-based framework. BS2 was not assessed from the available evidence. Details ▾Hide ▴
Rule
Use BS2 only with qualifying point-based observations under the BRCA2 specification.
Evidence considered
- BRCA2 ENIGMA BS2 uses a recessive-disease observation framework rather than simple population presence.
Still missing
- No BS2 point-scoring observations were identified.
Sources
BS4 No quantitative lack-of-segregation likelihood ratio meeting ENIGMA BS4 thresholds was identified for this variant. BS4 was not assessed from the available evidence. Details ▾Hide ▴
Rule
BS4 requires quantitative lack-of-segregation evidence reaching ENIGMA likelihood-ratio thresholds.
Evidence considered
- Reviewed BRCA2 multifactorial resources did not yield a usable BS4 likelihood ratio for this exact variant.
Still missing
- No non-segregation likelihood ratio was identified.
Sources
BP5 No exact-variant clinical-history likelihood ratio meeting ENIGMA BP5 thresholds was identified. The reviewed BRCA2 clinical-history likelihood-ratio table did not provide a usable entry for this variant, so BP5 was not assessed. Details ▾Hide ▴
Rule
BP5 in BRCA2 ENIGMA requires a qualifying multifactorial clinical likelihood ratio in the benign direction.
Evidence considered
- The BRCA2 Li 2020 clinical-history LR workbook was reviewed without a usable exact-variant match.
Still missing
- No exact-variant clinical-history LR was identified.
- No combined multifactorial LR qualifying for BP5 was recovered.
Sources
Not applicable · 11· recorded as not applicable Show reasons ▾Hide reasons ▴
PS2 VCEPPS2 is not used in this BRCA2 ENIGMA framework. Details ▾Hide ▴
VCEP rule
Not applicable in the BRCA2 ENIGMA specification.
Evidence considered
- PS2 is marked not applicable in the BRCA2 specification.
Sources
PM1 VCEPPM1 is not applied as an independent criterion in the BRCA2 ENIGMA framework because domain information is incorporated into the bioinformatic code logic instead. Details ▾Hide ▴
VCEP rule
Not applicable in the BRCA2 ENIGMA specification.
Evidence considered
- The BRCA2 ENIGMA specification marks PM1 as not applicable.
Sources
PM4 VCEPPM4 is not used in this BRCA2 ENIGMA framework. Details ▾Hide ▴
VCEP rule
Not applicable in the BRCA2 ENIGMA specification.
Evidence considered
- PM4 is marked not applicable in the BRCA2 specification.
Sources
PM5 N/AFor BRCA2 in this ENIGMA framework, PM5 is repurposed for protein-truncating variant logic rather than classic same-residue missense comparisons. Because this is a missense variant, PM5 is not applicable. Details ▾Hide ▴
Rule
BRCA2 PM5 is used for qualifying truncating variants, not classic missense same-residue logic.
Evidence considered
- pm5_candidates.json designates BRCA2 PM5 mode as PTC-specific and not eligible for classic same-residue missense PM5.
Sources
cspec ↗pm5_candidates
PM6 VCEPPM6 is not used in this BRCA2 ENIGMA framework. Details ▾Hide ▴
VCEP rule
Not applicable in the BRCA2 ENIGMA specification.
Evidence considered
- PM6 is marked not applicable in the BRCA2 specification.
Sources
PP2 VCEPPP2 is not used in this BRCA2 ENIGMA framework. Details ▾Hide ▴
VCEP rule
Not applicable in the BRCA2 ENIGMA specification.
Evidence considered
- PP2 is marked not applicable in the BRCA2 specification.
Sources
PP5 VCEPPP5 is not used in this BRCA2 ENIGMA framework. Details ▾Hide ▴
VCEP rule
Not applicable in the BRCA2 ENIGMA specification.
Evidence considered
- PP5 is explicitly not for use in this VCEP framework.
Sources
BP2 VCEPBP2 is not used in this BRCA2 ENIGMA framework. Details ▾Hide ▴
VCEP rule
Not applicable in the BRCA2 ENIGMA specification.
Evidence considered
- BP2 is marked not applicable in the BRCA2 specification.
Sources
BP3 VCEPBP3 is not used in this BRCA2 ENIGMA framework. Details ▾Hide ▴
VCEP rule
Not applicable in the BRCA2 ENIGMA specification.
Evidence considered
- BP3 is marked not applicable in the BRCA2 specification.
Sources
BP6 VCEPBP6 is not used in this BRCA2 ENIGMA framework. Details ▾Hide ▴
VCEP rule
Not applicable in the BRCA2 ENIGMA specification.
Evidence considered
- BP6 is marked not applicable in the BRCA2 specification.
Sources
BP7 N/ABP7 does not apply because this is a missense variant. In the BRCA2 ENIGMA framework, BP7 is reserved for specific synonymous, intronic, or RNA-only contexts. Details ▾Hide ▴
Rule
BP7 is for qualifying synonymous, intronic, or RNA-only evidence contexts, not a missense substitution of this type.
Evidence considered
- Variant type is missense
- p.(Gly2748Ser).
Sources
Identifiers
- Gene
- BRCA2
- Transcript
- NM_000059.3
- Coding (HGVS c.)
- NM_000059.3:c.8242G>A
- Protein (HGVS p.)
- NP_000050.2:p.(Gly2748Ser)
- GRCh38
- chr13:32363444 G>A
- GRCh37
- chr13:32937581 G>A
- ClinVar
- 3636537, 409429
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
6 / 1,614,064 alleles
AF 3.72e-06 · 0 homozygotes · FAF 5.53e-06
gnomAD v2.1
3 / 249,070 alleles
AF 1.2e-05 · 0 homozygotes · FAF 9.58e-06
By genetic ancestry
gnomAD v4.1
AF 3.7e-06 · 6 / 1,614,064 alleles · 0 hom · FAF 5.5e-06
| Admixed American2 / 60,012 | 3.3e-05 |
| European (non-Finnish)4 / 1,180,012 | 3.4e-06 |
0 alternate alleles recorded in 8 other groups: Remaining individuals, European (Finnish), Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish, African/African American.
gnomAD v2.1
AF 1.2e-05 · 3 / 249,070 alleles · 0 hom · FAF 9.6e-06
| Admixed American2 / 34,574 | 5.8e-05 |
| European (Finnish)1 / 21,634 | 4.6e-05 |
0 alternate alleles recorded in 6 other groups: African/African American, Ashkenazi Jewish, East Asian, European (non-Finnish), Remaining individuals, South Asian.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 3.71732e-06; MAF= 0.00037%, 6/1614064 alleles, homozygotes = 0) and has highest observed frequency in the Admixed American population (AF= 3.33267e-05; MAF= 0.00333%, 2/60012 alleles, homozygotes = 0); grpmax FAF= 5.53e-06.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.20448e-05; MAF= 0.00120%, 3/249070 alleles, homozygotes = 0) and has highest observed frequency in the Admixed American population (AF= 5.78469e-05; MAF= 0.00578%, 2/34574 alleles, homozygotes = 0); grpmax FAF= 9.58e-06.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.842
- BayesDel
- 0.454
How the predictions were used
PP3 SupportingThis missense variant lies within the BRCA2 DNA-binding domain, a clinically important functional region used by the ENIGMA bioinformatic framework. BayesDel no-AF is 0.454479, which is above the ENIGMA PP3 threshold of 0.30, SpliceAI shows no significant splice effect with a maximum delta score of 0.06, and REVEL is 0.842; together these findings support a damaging protein effect and meet PP3 at supporting strength. Details ▾Hide ▴
Rule
For BRCA2 missense variants inside a clinically important domain, apply PP3_Supporting when BayesDel no-AF >= 0.30; splicing prediction is considered separately.
Evidence considered
- Protein position 2748 lies within the BRCA2 DNA-binding domain aa 2481-3186.
- BayesDel no-AF 0.454479 >= 0.30.
- SpliceAI max delta 0.06.
- REVEL 0.842.
Sources
BP4 BP4 is not met. Although SpliceAI predicts no significant splice impact with a maximum delta score of 0.06, the variant is inside the BRCA2 DNA-binding domain and the BayesDel no-AF score is 0.454479, which is above the BP4 benign threshold of 0.18 and instead supports predicted protein impact. Details ▾Hide ▴
Rule
BP4 for BRCA2 missense variants in clinically important domains requires BayesDel no-AF <= 0.18 and SpliceAI <= 0.1.
Evidence considered
- BayesDel no-AF 0.454479 > 0.18.
- SpliceAI max delta 0.06 <= 0.1.
- REVEL 0.842.
Sources
BP7 N/ABP7 does not apply because this is a missense variant. In the BRCA2 ENIGMA framework, BP7 is reserved for specific synonymous, intronic, or RNA-only contexts. Details ▾Hide ▴
Rule
BP7 is for qualifying synonymous, intronic, or RNA-only evidence contexts, not a missense substitution of this type.
Evidence considered
- Variant type is missense
- p.(Gly2748Ser).
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.06). REVEL score = 0.842. BayesDel score = 0.454479.
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.No paper-specific finding is recorded.
-
PMID 17924331 ↗A systematic genetic assessment of 1,433 sequence variants of unknown clinical significance in the BRCA1 and BRCA2 breast cancer-predisposition genes.Easton DF et al. · 2007No paper-specific finding is recorded.
-
PMID 18451181 ↗Functional assays for classification of BRCA2 variants of uncertain significance.Farrugia DJ et al. · 2008No paper-specific finding is recorded.
-
PMID 21671020 ↗Effect of the overexpression of BRCA2 unclassified missense variants on spontaneous homologous recombination in human cells.Balia C et al. · 2011No paper-specific finding is recorded.
-
PMID 23108138 ↗A classification model for BRCA2 DNA binding domain missense variants based on homology-directed repair activity.No paper-specific finding is recorded.
-
PMID 23328489 ↗Effect of the expression of BRCA2 on spontaneous homologous recombination and DNA damage-induced nuclear foci in Saccharomyces cerevisiae.No paper-specific finding is recorded.
-
PMID 25146914 ↗An efficient pipeline for the generation and functional analysis of human BRCA2 variants of uncertain significance.No paper-specific finding is recorded.
-
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
6 / 1,614,064 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.060
Open source ↗
ClinVar
7 Likely pathogenic · 1 Pathogenic · 1 likely pathogenic
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/409429/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/13-32937581-G-A?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr13-32363444-G-A?dataset=gn…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000059.3%3Ac.8242…
- OncoKB ↗www.oncokb.org/gene/BRCA2/G2748S
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=BRCA2+c.8242G%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= 3.71732e-06; MAF= 0.00037%, 6/1614064 alleles, homozygotes = 0) and has highest observed frequency in the Admixed American population (AF= 3.33267e-05; MAF= 0.00333%, 2/60012 alleles, homozygotes = 0); grpmax FAF= 5.53e-06.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.20448e-05; MAF= 0.00120%, 3/249070 alleles, homozygotes = 0) and has highest observed frequency in the Admixed American population (AF= 5.78469e-05; MAF= 0.00578%, 2/34574 alleles, homozygotes = 0); grpmax FAF= 9.58e-06.
ClinVar
This variant has been reported in ClinVar as Likely pathogenic (7 clinical laboratories) and as Pathogenic (1 clinical laboratory) and as likely pathogenic (1 clinical laboratory) and as Uncertain Significance by ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel, ClinGen (expert panel). (ClinVarID = 409429)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.06). REVEL score = 0.842. BayesDel score = 0.454479.
Functional
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Loss-of-function; curated oncogenicity label: Likely Oncogenic.
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.