About BRCA2
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
BRCA2 c.4284dup, p.(Gln1429SerfsTer9)
Classification
Pathogenic
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is pathogenic. Select a step to read what it means.
Pathogenic.A pathogenic 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: 4
Benign evidence criteria: 0
Pathogenic criteria applied · 4
PVS1Very strong
PVS1 · very strong
NM_000059.4:c.4284dup is a frameshift duplication in BRCA2 exon 11 (c.1910-6841) predicted to cause a premature termination codon at p.(Gln1429SerfsTer9). Per ENIGMA Specifications Table 4, BRCA2 exon 11 PTC variants are assigned PVS1 (very strong). BRCA2 loss of function is an established disease mechanism for hereditary breast and ovarian cancer. NMD is expected given the truncation occurs well upstream of the final exon.
PM5Strong
PM5 · strong
Per ENIGMA Specifications Table 4, BRCA2 exon 11 PTC variants are assigned PM5_Strong (PTC). Exon 11 is not in the PM5_N/A exclusion list (E12, E27, E6). This criterion provides additional weight for PTC variants already annotated as PVS1, reflecting the established pathogenicity of other PTC variants in this exon.
PP4Supporting
PP4 · supporting
Per ENIGMA PP4, the clinical history likelihood ratio from Li et al. 2020 (PMID:31853058) for BRCA2 c.4284dup is LR=2.23 based on 21 probands, exceeding the PP4_Supporting threshold of LR≥2.08. This indicates that the personal and family cancer history of carriers is more consistent with a pathogenic variant than with a benign finding.
PP5Supporting
PP5 · supporting
Expert panel Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) classified as Pathogenic.
Benign criteria applied · 0
No benign criterion marked as applied in the recorded assessment.
Recorded classification: Pathogenic
ENIGMA BRCA1/BRCA2 v1.2 Table 3 criteria combination rules applied to adjudicated criteria from criteria_assessment.json. The variant has PVS1 (very strong), PM5_Strong (strong), PP4_Supporting, and PP5_Supporting. Under Table 3, 1×Very Strong + ≥1×Strong → Pathogenic, and also 1×Very Strong + ≥2×Supporting → Pathogenic. Both independently meet the Pathogenic threshold. No benign criteria are met, so no conflicting-evidence point calculation is required.
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
17 / 1,598,752 alleles
gnomAD v4.1: 17 / 1,598,752 alleles. Recorded AF 1.06333e-05. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 4.09122e-06; MAF= 0.00041%, 1/244426 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 8.96411e-06; MAF= 0.00090%, 1/111556 alleles, homozygotes = 0).
gnomAD-Canada
Not available in 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
34 reported laboratory submissions
33 Pathogenic · 1 pathogenic. ClinVar API review status: reviewed by expert panel.
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.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
2 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV66465921, n = 2 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, with the data and sources behind each one.
28 criteria with recorded statuses: 4 met · 6 not met · 6 not assessed · 12 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.4284dup is a frameshift duplication in BRCA2 exon 11, predicted to generate a premature termination codon at p.(Gln1429SerfsTer9) with expected NMD.
PVS1 (very strong) is applied per ENIGMA Specifications Table 4, which assigns PVS1 to BRCA2 exon 11 PTC variants. BRCA2 loss of function is an established mechanism for hereditary breast and ovarian cancer.
PM5_Strong (PTC) is applied per ENIGMA Table 4, reflecting that exon 11 harbors multiple proven pathogenic PTC variants supporting additional weight beyond PVS1.
PP4_Supporting is applied based on clinical history likelihood ratio of 2.23 from 21 probands in the Li et al. 2020 cohort, exceeding the ENIGMA PP4 supporting threshold of LR ≥ 2.08.
PP5_Supporting is applied per standing adjudication rule: ClinVar classifies this variant as Pathogenic with ENIGMA expert panel review (3-star), warranting PP5 at supporting strength.
Under ENIGMA Table 3 combining rules, 1×PVS1 (very strong) + 1×PM5_Strong (strong) satisfies the pathogenic classification threshold (1×Very Strong + ≥1×Strong). Additionally, 1×Very Strong + ≥2×Supporting (PP4 + PP5) independently meets the pathogenic threshold.
Final classification: PATHOGENIC, consistent with the ENIGMA expert panel classification in ClinVar (Variation ID 37892).
No criteria match.
Met · 4
PVS1 Very strongNM_000059.4:c.4284dup is a frameshift duplication in BRCA2 exon 11 (c.1910-6841) predicted to cause a premature termination codon at p.(Gln1429SerfsTer9). Per ENIGMA Specifications Table 4, BRCA2 exon 11 PTC variants are assigned PVS1 (very strong). BRCA2 loss of function is an established disease mechanism for hereditary breast and ovarian cancer. NMD is expected given the truncation occurs well upstream of the final exon. Details ▾Hide ▴
Evidence considered
- BRCA2 exon 11 PTC assigned PVS1 per ENIGMA Specifications Table 4
- Frameshift duplication c.4284dup → p.(Gln1429SerfsTer9)
- stop at codon 1437 of 3418
- NMD expected: truncation >50-55 nucleotides upstream of last exon-exon junction
- LOF established disease mechanism for BRCA2
Sources
PM5 StrongPer ENIGMA Specifications Table 4, BRCA2 exon 11 PTC variants are assigned PM5_Strong (PTC). Exon 11 is not in the PM5_N/A exclusion list (E12, E27, E6). This criterion provides additional weight for PTC variants already annotated as PVS1, reflecting the established pathogenicity of other PTC variants in this exon. Details ▾Hide ▴
Evidence considered
- BRCA2 exon 11 PTC assigned PM5_Strong (PTC) per ENIGMA Table 4
- Exon 11 harbors multiple known pathogenic PTC variants
Sources
vcep_specifications_table4_v1_2_2024_11_18cspec ↗
PP4 SupportingPer ENIGMA PP4, the clinical history likelihood ratio from Li et al. 2020 (PMID:31853058) for BRCA2 c.4284dup is LR=2.23 based on 21 probands, exceeding the PP4_Supporting threshold of LR≥2.08. This indicates that the personal and family cancer history of carriers is more consistent with a pathogenic variant than with a benign finding. Details ▾Hide ▴
Evidence considered
- Clinical history LR = 2.23
- N=21 probands (Li et al. 2020
- PMID:31853058)
- PP4_Supporting threshold: LR ≥ 2.08
Sources
PP5 SupportingExpert panel Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) classified as Pathogenic. Details ▾Hide ▴
Not met · 6 · evaluated, threshold not reached
PS3 No variant-specific functional studies were identified for NM_000059.4:c.4284dup. ENIGMA Specifications Table 9 (curated functional assay results) covers missense and synonymous variants only and does not list c.4284dup. Full-text review of available publications did not identify functional characterization of this variant. General domain-level or truncation-mechanism inference does not satisfy PS3 requirements. Details ▾Hide ▴
Evidence considered
- ENIGMA Table 9: no entry for c.4284dup (table limited to missense/synonymous variants)
- No variant-specific functional assay data identified in literature
Still missing
- No functional studies testing this specific variant
Sources
vcep_specifications_table9_v1_2_2024_11_18
PM2 ENIGMA PM2_Supporting requires the variant to be absent from gnomAD v2.1 (non-cancer, exome only subset) and gnomAD v3.1 (non-cancer). This variant is present in gnomAD v2.1 with 1 allele (AF=4.09e-6, NFE_SEU subpopulation) and in gnomAD v4.1 with 17 alleles (grpmax FAF=6.94e-6). The variant is not absent and therefore does not meet the ENIGMA PM2 criterion. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: 1/244
- 426 alleles (AF=4.09e-6
- NFE_SEU)
- gnomAD v4.1: 17/1
- 598
- 752 alleles (AF=1.06e-5
- grpmax FAF=6.94e-6)
- ENIGMA PM2 requires absence
- variant is present
Sources
PP3 SpliceAI predicts no splice impact (max delta score = 0.00). The variant is a frameshift duplication, which falls outside ENIGMA PP3 applicability (PP3 is defined for missense/in-frame variants in functional domains with BayesDel ≥0.30, or for variants with SpliceAI ≥0.20). Neither threshold is met. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.00 (no splice impact predicted)
- Frameshift variant not eligible for BayesDel-based PP3
Sources
BA1 ENIGMA BA1 requires filter allele frequency (FAF) > 0.001 (0.1%) in gnomAD non-cancer populations. The grpmax FAF for this variant is 6.94e-6 (0.00069%) in gnomAD v4.1, which is approximately 144-fold below the BA1 threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 grpmax FAF = 6.94e-6
- far below BA1 threshold of 0.001
Sources
BS1 ENIGMA BS1_Supporting requires FAF > 0.00002 (0.002%) and BS1_Strong requires FAF > 0.0001 (0.01%). The grpmax FAF is 6.94e-6, which falls below even the BS1_Supporting threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 grpmax FAF = 6.94e-6 (below BS1_Supporting threshold of 2e-5)
Sources
BP5 The clinical history LR from Li et al. 2020 (PMID:31853058) is 2.23, which favors pathogenicity. ENIGMA BP5 requires LR ≤0.48 for supporting benign evidence. An LR >1.0 is incompatible with BP5 application. Details ▾Hide ▴
Evidence considered
- Clinical history LR = 2.23 (pathogenic direction
- BP5 not applicable)
Sources
Not assessed · 6 · no assessment recorded
PS4 ENIGMA PS4 requires a formal case-control study with odds ratio ≥4 and lower confidence interval excluding 2.0. No dedicated case-control study for c.4284dup was identified in the evidence brief or literature review. The variant has been observed in 21 probands in the Li et al. 2020 clinical history cohort, but this does not constitute a case-control comparison. Details ▾Hide ▴
Evidence considered
- No formal case-control study available for this variant
Still missing
- Formal case-control data needed for PS4
Sources
PP1 ENIGMA PP1 requires quantitative cosegregation analysis with likelihood ratio ≥2.08. No cosegregation data for NM_000059.4:c.4284dup was identified in the evidence brief or literature review. Details ▾Hide ▴
Evidence considered
- No cosegregation analysis data available for this variant
Still missing
- Cosegregation data needed for PP1
Sources
BS2 ENIGMA BS2 requires evaluation of Fanconi Anemia phenotype and point-based scoring per Specifications Table 8. No Fanconi Anemia phenotype data was available for this variant. Details ▾Hide ▴
Evidence considered
- No Fanconi Anemia phenotype information available
Still missing
- Observations in trans with other BRCA2 PTC variants needed for BS2 assessment
Sources
BS3 ENIGMA Table 9 (curated functional assay results for BS3) covers missense and synonymous variants only. No BS3-relevant functional data for this frameshift variant was identified. Details ▾Hide ▴
Evidence considered
- ENIGMA Table 9: no entry for c.4284dup
Still missing
- No functional data demonstrating normal protein function
Sources
vcep_specifications_table9_v1_2_2024_11_18
BS4 ENIGMA BS4 requires quantitative lack-of-segregation analysis with likelihood ratio ≤0.48. No segregation data for c.4284dup was identified. Details ▾Hide ▴
Evidence considered
- No segregation data available
Still missing
- Lack-of-segregation LR data needed for BS4
Sources
BP7 ENIGMA BP7 requires well-established in vitro/in vivo functional studies showing no damaging effect on mRNA transcript profile (mRNA assay only). No mRNA assay data for c.4284dup was identified. Details ▾Hide ▴
Evidence considered
- No mRNA transcript profile data available
Still missing
- mRNA assay data needed for BP7 assessment
Sources
Not applicable · 12· recorded as not applicable Show reasons ▾Hide reasons ▴
PS1 N/AENIGMA PS1 applies only to missense substitutions or variants with predicted splicing impact comparable to a known pathogenic variant. NM_000059.4:c.4284dup is a frameshift duplication and is not eligible for PS1 per the ENIGMA specification. Details ▾Hide ▴
Sources
PS2 VCEPENIGMA specification marks PS2 as Not Applicable for BRCA2. Details ▾Hide ▴
Sources
PM1 VCEPENIGMA specification marks PM1 as Not Applicable for BRCA2. Details ▾Hide ▴
Sources
PM4 VCEPENIGMA specification marks PM4 as Not Applicable for BRCA2. Details ▾Hide ▴
Sources
PM6 VCEPENIGMA specification marks PM6 as Not Applicable for BRCA2. Details ▾Hide ▴
Sources
PP2 VCEPENIGMA specification marks PP2 as Not Applicable for BRCA2. Details ▾Hide ▴
Sources
BP1 N/AENIGMA BP1 applies to silent substitutions, missense variants, or in-frame insertions/deletions outside clinically important functional domains with no splicing predicted. NM_000059.4:c.4284dup is a frameshift duplication and is not eligible for BP1. Details ▾Hide ▴
Sources
BP2 VCEPENIGMA specification marks BP2 as Not Applicable for BRCA2. Details ▾Hide ▴
Sources
BP3 VCEPENIGMA specification marks BP3 as Not Applicable for BRCA2. Details ▾Hide ▴
Sources
BP4 N/AENIGMA BP4 applies to missense or in-frame insertion/deletion/delins variants inside a clinically important functional domain with no predicted impact. NM_000059.4:c.4284dup is a frameshift duplication and is not eligible for BP4. Details ▾Hide ▴
Sources
BP6 VCEPClinVar classification for this variant is Pathogenic (expert panel). BP6 requires a benign or likely benign consensus. The standing PP5/BP6 rule applies PP5_Supporting for 3-star EP pathogenic classifications; BP6 is not applicable to variants classified as pathogenic by expert panel. Details ▾Hide ▴
PS5 N/ANot in the assess list; ENIGMA specification does not define PS5 for BRCA2. Details ▾Hide ▴
No further detail was recorded.
Identifiers
- Gene
- BRCA2
- Transcript
- NM_000059.4
- Coding (HGVS c.)
- NM_000059.4:c.4284dup
- Protein (HGVS p.)
- NP_000050.3:p.(Gln1429SerfsTer9)
- GRCh38
- chr13:32338633 A>AT
- GRCh37
- chr13:32912770 A>AT
- ClinVar
- 37892
- COSMIC
- COSV66465921
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
17 / 1,598,752 alleles
AF 1.06e-05 · 0 homozygotes · FAF 6.94e-06
gnomAD v2.1
1 / 244,426 alleles
AF 4.09e-06 · 0 homozygotes
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 1.1e-05 · 17 / 1,598,752 alleles · 0 hom · FAF 6.9e-06
| South Asian2 / 88,534 | 2.3e-05 |
| African/African American1 / 74,480 | 1.3e-05 |
| European (non-Finnish)14 / 1,170,438 | 1.2e-05 |
0 alternate alleles recorded in 7 other groups: Remaining individuals, Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, Ashkenazi Jewish.
gnomAD v2.1
AF 4.1e-06 · 1 / 244,426 alleles · 0 hom
| European (non-Finnish)1 / 111,556 | 9e-06 |
0 alternate alleles recorded in 7 other groups: African/African American, Admixed American, Ashkenazi Jewish, East Asian, European (Finnish), Remaining individuals, South Asian.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 1.06333e-05; MAF= 0.00106%, 17/1598752 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 2.25902e-05; MAF= 0.00226%, 2/88534 alleles, homozygotes = 0); grpmax FAF= 6.94e-06.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 4.09122e-06; MAF= 0.00041%, 1/244426 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 8.96411e-06; MAF= 0.00090%, 1/111556 alleles, homozygotes = 0).
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
PP3 SpliceAI predicts no splice impact (max delta score = 0.00). The variant is a frameshift duplication, which falls outside ENIGMA PP3 applicability (PP3 is defined for missense/in-frame variants in functional domains with BayesDel ≥0.30, or for variants with SpliceAI ≥0.20). Neither threshold is met. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.00 (no splice impact predicted)
- Frameshift variant not eligible for BayesDel-based PP3
Sources
BP7 ENIGMA BP7 requires well-established in vitro/in vivo functional studies showing no damaging effect on mRNA transcript profile (mRNA assay only). No mRNA assay data for c.4284dup was identified. Details ▾Hide ▴
Evidence considered
- No mRNA transcript profile data available
Still missing
- mRNA assay data needed for BP7 assessment
Sources
BP4 N/AENIGMA BP4 applies to missense or in-frame insertion/deletion/delins variants inside a clinically important functional domain with no predicted impact. NM_000059.4:c.4284dup is a frameshift duplication and is not eligible for BP4. Details ▾Hide ▴
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
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 31853058 ↗Li et al. 2020 BRCA1/2 clinical-history likelihood-ratio modelLi et al. 2020 classified BRCA1/2 VUS using personal and family cancer history from a multigene panel testing cohort. BRCA2 c.4284dupT was evaluated with a clinical history likelihood ratio of 2.23 (LOG(LR)=0.80) based on 21 probands, supporting pathogenicity at the PP4_Supporting level.→ PP4 Names this variant
Source detail
BRCA2 c.4284dupT LOG(LR)=0.8019, N_Probands=21, LR=2.23
Location Clinical history LR spreadsheet (MOESM3): BRCA2 c.4284dupT, LR=2.23, N=21
Other recorded publications
-
PMID 10570174 ↗Truncated BRCA2 is cytoplasmic: implications for cancer-linked mutations.Spain et al. 1999 demonstrated that BRCA2 nuclear localization depends on two NLSs within the final 156 residues, and showed that the endogenous cancer-associated truncation mutant 6174delT is cytoplasmic. NM_000059.4:c.4284dup was not specifically studied or mentioned in this paper.Does not name this variant
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PMID 11239455 ↗BRCA2 is required for homology-directed repair of chromosomal breaks.Moynahan et al. 2001 demonstrated that BRCA2 is required for homology-directed repair of chromosomal breaks. NM_000059.4:c.4284dup was not identified in this paper.Does not name this variant
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PMID 20878484 ↗A new mutation of BRCA2 gene in an Italian healthy woman with familial breast cancer history.Palmieri et al. 2010 reported a new BRCA2 mutation in an Italian healthy woman with familial breast cancer history. Full text was not available for review; abstract does not mention NM_000059.4:c.4284dup.Does not name this variant
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PMID 22193408 ↗BRCA1 and BRCA2: different roles in a common pathway of genome protection.Roy et al. 2012 reviewed BRCA1 and BRCA2 roles in genome protection. NM_000059.4:c.4284dup was not identified in this paper.Does not name this variant
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PMID 24312913 ↗A comprehensive focus on global spectrum of BRCA1 and BRCA2 mutations in breast cancer.Karami and Mehdipour 2013 reviewed the global spectrum of BRCA1 and BRCA2 mutations in breast cancer. A match for '4284delGA' was found but refers to a BRCA1 variant; NM_000059.4:c.4284dup (BRCA2) was not identified.Does not name this variant
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PMID 16199546 ↗Large genomic deletions inactivate the BRCA2 gene in breast cancer families.Agata S et al. · 2005Agata et al. 2005 investigated large genomic deletions in BRCA2 in breast cancer families. NM_000059.4:c.4284dup was not identified in this paper.Does not name this variant
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PMID 20104584 ↗Characterization of BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance in unilateral and bilateral breast cancer: the WECARE study.Borg A et al. · 2010Borg et al. 2010 (WECARE Study) characterized BRCA1/2 deleterious mutations and VUS in contralateral and unilateral breast cancer. NM_000059.4:c.4284dup was not identified among the reported variants in this paper.Does not name this variant
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PMID 22085629 ↗Prevalence of BRCA1 and BRCA2 mutations in unselected breast cancer patients from Greece.Koumpis C et al. · 2011Koumpis et al. 2011 assessed BRCA1/2 mutation prevalence in unselected Greek breast cancer patients. NM_000059.4:c.4284dup was not identified in this paper.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
17 / 1,598,752 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
33 Pathogenic · 1 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/37892/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/13-32912770-A-AT?dataset=gnom…
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr13-32338633-A-AT?dataset=g…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/13-32338633-A-AT
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000059.4%3Ac.4284…
- OncoKB ↗www.oncokb.org/gene/BRCA2/Q1429Sfs*9
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=140311802
- 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= 1.06333e-05; MAF= 0.00106%, 17/1598752 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 2.25902e-05; MAF= 0.00226%, 2/88534 alleles, homozygotes = 0); grpmax FAF= 6.94e-06.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 4.09122e-06; MAF= 0.00041%, 1/244426 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 8.96411e-06; MAF= 0.00090%, 1/111556 alleles, homozygotes = 0).
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Pathogenic (33 clinical laboratories) and as pathogenic (1 clinical laboratory) and as Pathogenic by Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) (expert panel). (ClinVarID = 37892)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
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 previously been reported in somatic cancers (COSMIC; COSV66465921, n = 2 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.