About BRCA2
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
BRCA2 c.5218_5223del, p.(Leu1740_Ser1741del)
Classification
Benign
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is benign. Select a step to read what it means.
Benign.A benign classification under the recorded framework.
In plain language
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.
LYFE Sciences is an AI system, and it can make mistakes.
Criteria may be applied incorrectly, sources may be misread, and a
confident-looking classification can still be wrong.
Double-check every criterion and its underlying evidence
before relying on any call.
01The reasoning
How it was classified
The recorded framework is ClinGen BRCA2 VCEP v1.2. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.
Recorded applied criteria
The applied criteria and their strengths are shown as assessed under the stated framework.
Pathogenic evidence criteria: 0
Benign evidence criteria: 2
Pathogenic criteria applied · 0
No pathogenic criterion marked as applied in the recorded assessment.
Benign criteria applied · 2
BS1Strong
BS1 · strong
The gnomAD v2.1 exome grpmax filter allele frequency (FAF) is 0.000106 (0.0106%), which exceeds the ENIGMA BS1 Strong threshold of FAF > 0.01% (FAF > 0.0001) in non-cancer, non-founder populations. This is observed primarily in the East Asian subpopulation (6/19,916 alleles, AF = 0.030%).
BP1Strong
BP1 · strong
This is an in-frame deletion (p.Leu1740_Ser1741del) located outside the two ENIGMA-defined clinically important functional domains (PALB2 binding aa 10–40; DNA binding aa 2481–3186). SpliceAI predicts no splicing impact (max delta = 0.00, ≤ 0.1). ENIGMA BP1_Strong criteria are satisfied: in-frame deletion outside a clinically important domain with no splicing predicted.
Recorded classification: Benign
ENIGMA BRCA2 Table 3 combining rules applied to adjudicated criteria. Two Strong Benign criteria are met: BS1_Strong (gnomAD grpmax FAF = 0.0106% exceeds ENIGMA BS1 Strong threshold of >0.01%) and BP1_Strong (in-frame deletion p.Leu1740_Ser1741del outside clinically important functional domains with SpliceAI max delta = 0.00, no splicing impact). The ENIGMA Table 3 benign rule 'Strong (Benign) >= 2' is satisfied. No pathogenic criteria are met, so there is no conflicting evidence to adjudicate.
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
10 / 1,609,336 alleles
gnomAD v4.1: 10 / 1,609,336 alleles. Recorded AF 6.21374e-06. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 2.49896e-05; MAF= 0.00250%, 7/280116 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 0.000301265; MAF= 0.03013%, 6/19916 alleles, homozygotes = 0); grpmax FAF= 0.00010642.
gnomAD-Canada
Not available in 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
10 reported laboratory submissions
9 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, with the data and sources behind each one.
28 criteria with recorded statuses: 2 met · 13 not met · 0 not assessed · 13 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_000059.3:c.5218_5223del (p.Leu1740_Ser1741del) is an in-frame deletion of 6 nucleotides in BRCA2 exon 11, removing two amino acids (Leu1740 and Ser1741) from a region between BRC repeats 5 and 6, outside the ENIGMA-defined clinically important functional domains.
The variant is present in gnomAD population databases at a grpmax filter allele frequency of 0.0106% (FAF = 0.000106) in gnomAD v2.1 exomes, exceeding the ENIGMA BS1 Strong threshold of > 0.01% (FAF > 0.0001). Highest subpopulation frequency is in East Asians (AF = 0.030%, 6/19,916 alleles). No homozygotes observed.
As an in-frame deletion located outside the ENIGMA-defined clinically important functional domains (PALB2 binding aa 10–40; DNA binding aa 2481–3186) with no splicing impact predicted (SpliceAI max delta = 0.00), ENIGMA BP1_Strong is met: in-frame deletion outside a clinically important domain without splicing prediction.
Clinical-history likelihood ratio from Li et al. 2020 (PMID:31853058) is 0.77 (8 probands), falling in the neutral zone. Neither PP4 nor BP5 is applicable.
This variant has been reported in ClinVar as Uncertain significance by 9 clinical laboratories and Likely benign by 1 clinical laboratory (ClinVar Variation ID: 51824; review status: criteria provided, single submitter). No expert panel classification exists.
No functional studies, case-control data, segregation data, or variant-specific publications were identified for this variant. Five publications were reviewed in full text; none mention NM_000059.3:c.5218_5223del.
Applying the ENIGMA Table 3 combining rules: two Strong Benign criteria (BS1 + BP1) satisfy the Benign classification threshold (Strong Benign ≥ 2). This variant is classified as BENIGN.
No criteria match.
Met · 2
BS1 StrongThe gnomAD v2.1 exome grpmax filter allele frequency (FAF) is 0.000106 (0.0106%), which exceeds the ENIGMA BS1 Strong threshold of FAF > 0.01% (FAF > 0.0001) in non-cancer, non-founder populations. This is observed primarily in the East Asian subpopulation (6/19,916 alleles, AF = 0.030%). Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 exome grpmax FAF = 0.00010642 (> 0.0001 ENIGMA BS1 Strong threshold)
- 7 total alleles in gnomAD v2.1 (280
- 116 alleles)
- 0 homozygotes
- Highest in East Asian: 6/19
- 916 (0.030%)
Sources
BP1 StrongThis is an in-frame deletion (p.Leu1740_Ser1741del) located outside the two ENIGMA-defined clinically important functional domains (PALB2 binding aa 10–40; DNA binding aa 2481–3186). SpliceAI predicts no splicing impact (max delta = 0.00, ≤ 0.1). ENIGMA BP1_Strong criteria are satisfied: in-frame deletion outside a clinically important domain with no splicing predicted. Details ▾Hide ▴
Evidence considered
- In-frame deletion at aa 1740–1741
- outside PALB2 binding (aa 10–40) and DNA binding (aa 2481–3186) domains
- SpliceAI max delta = 0.00
- no splicing impact predicted
Sources
Not met · 13 · evaluated, threshold not reached
PS3 No variant-specific or systematic-range functional data identified for NM_000059.3:c.5218_5223del. ENIGMA Table 9 (curated functional assays) covers only missense and synonymous BRCA2 variants; this in-frame deletion is not listed. Literature review of 5 publications identified no functional studies of this variant. Details ▾Hide ▴
Evidence considered
- ENIGMA Table 9 does not include this variant (missense/synonymous only)
- No functional data in any reviewed publication
Still missing
- No functional studies available for this in-frame deletion
Sources
vcep_specifications_table9_v1_2_2024_11_18cspec ↗
PS4 No case-control study demonstrating significantly increased prevalence of this variant in affected individuals versus controls has been identified. ENIGMA PS4 requires p ≤ 0.05 and OR ≥ 4. No such data available for this variant. Details ▾Hide ▴
Evidence considered
- No case-control data identified in literature or databases
Still missing
- No case-control study available
Sources
PM2 ENIGMA PM2 (Supporting) requires absence from gnomAD controls. This variant is present in gnomAD v2.1 (7/280,116 alleles, AF = 2.50 × 10⁻⁵) and gnomAD v4.1 (10/1,609,336 alleles, AF = 6.21 × 10⁻⁶), with highest subpopulation frequency in East Asian (AF = 0.030% in v2.1). The variant is not absent from outbred population controls. Details ▾Hide ▴
Evidence considered
- Present in gnomAD v2.1: 7 alleles / 280
- 116 (AF = 2.50 × 10⁻⁵)
- Present in gnomAD v4.1: 10 alleles / 1
- 609
- 336 (AF = 6.21 × 10⁻⁶)
- Highest subpopulation: East Asian
- 6/19
- 916 (AF = 0.030%)
Sources
PP1 No co-segregation data available for this variant. ENIGMA PP1 requires quantitative co-segregation analysis with LR ≥ 2.08 for Supporting strength. Details ▾Hide ▴
Evidence considered
- No co-segregation data identified
Still missing
- No co-segregation analysis available
Sources
PP3 This in-frame deletion (p.Leu1740_Ser1741del) lies outside the two ENIGMA-defined clinically important functional domains (BRCA2 PALB2 binding domain aa 10–40; BRCA2 DNA binding domain aa 2481–3186). SpliceAI predicts no splicing impact (max delta = 0.00). PP3 requires either location inside a clinically important domain with BayesDel ≥ 0.30, or SpliceAI ≥ 0.2. Neither condition is met. Details ▾Hide ▴
Evidence considered
- Variant at aa 1740–1741
- outside PALB2 binding (aa 10–40) and DNA binding (aa 2481–3186) domains
- SpliceAI max delta = 0.00
- no splicing impact predicted
- BayesDel not available (indel
- not SNV)
Sources
PP4 Clinical-history likelihood ratio (LR) from Li et al. 2020 (PMID:31853058) for NM_000059.3:c.5218_5223del is 0.77 (LOG(LR) = −0.26; N = 8 probands). This falls within the ENIGMA neutral zone (>0.48 and <2.08), where neither PP4 nor BP5 is applied. Details ▾Hide ▴
Evidence considered
- LR = 0.77 (8 probands)
- neutral zone
- does not support pathogenicity
Sources
BA1 ENIGMA BA1 (Stand Alone) requires filter allele frequency (FAF) > 0.1% (FAF > 0.001) in gnomAD non-cancer populations. The grpmax FAF for this variant is 0.000106 (0.0106%), which is below the BA1 threshold. Details ▾Hide ▴
Evidence considered
- grpmax FAF = 0.000106 (0.0106%) < 0.001 (0.1%) threshold
Sources
BS2 ENIGMA BS2 requires observation of the variant in trans with a pathogenic variant in the absence of Fanconi Anemia phenotype, scored via a points system (Specifications Table 8). No such co-occurrence data or phenotype information is available for this variant. Details ▾Hide ▴
Evidence considered
- No Fanconi Anemia phenotype or trans co-occurrence data available
Still missing
- No trans co-occurrence or Fanconi Anemia phenotype data
Sources
BS3 No well-established functional studies demonstrate a neutral effect for this variant. ENIGMA Table 9 (curated functional assays) covers missense and synonymous variants only and does not include this in-frame deletion. Literature review identified no functional studies of this variant. Details ▾Hide ▴
Evidence considered
- ENIGMA Table 9 does not include this variant
- No functional studies identified in literature
Still missing
- No functional data available
Sources
vcep_specifications_table9_v1_2_2024_11_18cspec ↗
BS4 No lack-of-segregation data available for this variant. ENIGMA BS4 requires quantitative co-segregation analysis with LR ≤ 0.48 for Supporting strength. Details ▾Hide ▴
Evidence considered
- No segregation data available
Still missing
- No segregation data available
Sources
BP4 ENIGMA BP4 applies only to missense or in-frame variants located inside a clinically important functional domain with no predicted impact (BayesDel ≤ 0.18 and SpliceAI ≤ 0.1). This variant is at aa 1740–1741, outside the ENIGMA-defined clinically important domains (PALB2 binding aa 10–40; DNA binding aa 2481–3186). The domain location prerequisite is not satisfied. Details ▾Hide ▴
Evidence considered
- Variant outside clinically important functional domains
- SpliceAI max delta = 0.00
- no splicing impact
Sources
BP5 Clinical-history likelihood ratio (LR) from Li et al. 2020 (PMID:31853058) is 0.77. This falls within the ENIGMA neutral zone (>0.48 and <2.08), where neither PP4 nor BP5 is applied. Details ▾Hide ▴
Evidence considered
- LR = 0.77
- neutral zone
- does not support benignity
Sources
BP7 ENIGMA BP7 applies to (a) intronic/silent variants with mRNA assay evidence of no splicing impact (BP7_Strong RNA), or (b) silent variants inside a clinically important domain if BP4 is met (BP7_Supporting). This is an in-frame deletion, not a silent or intronic variant. No mRNA splicing assay data are available. Neither BP7 pathway applies. Details ▾Hide ▴
Evidence considered
- In-frame deletion
- not a silent or intronic variant
- No mRNA splicing assay data available
Still missing
- No mRNA assay data
Sources
Not applicable · 13· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANM_000059.3:c.5218_5223del is an in-frame deletion (p.Leu1740_Ser1741del) removing 6 nucleotides in exon 11. It is not a null variant (nonsense, frameshift, or canonical ±1,2 splice site) and therefore does not meet the ENIGMA BRCA2 PVS1 entry criteria as defined in Specifications Table 4. Details ▾Hide ▴
Evidence considered
- In-frame deletion of 2 amino acids (Leu1740_Ser1741)
- not a null variant
- ENIGMA PVS1 rules restricted to nonsense
- frameshift
- canonical splice site
- initiation codon
- and exon-level CNV
Sources
PS1 N/APS1 requires a missense substitution comparator or a variant with the same predicted splicing impact as a known pathogenic variant. This is an in-frame deletion, not a missense change, and SpliceAI predicts no splicing impact (max delta = 0.00). No applicable comparator exists. Details ▾Hide ▴
Evidence considered
- In-frame deletion
- not a missense substitution
- SpliceAI max delta = 0.00
- no splicing impact predicted
Sources
PS2 VCEPENIGMA BRCA2 specification marks PS2 as Not Applicable. Details ▾Hide ▴
No further detail was recorded.
PM1 VCEPENIGMA BRCA2 specification marks PM1 as Not Applicable. Details ▾Hide ▴
No further detail was recorded.
PM4 VCEPENIGMA BRCA2 specification marks PM4 as Not Applicable. Details ▾Hide ▴
No further detail was recorded.
PM5 N/AENIGMA repurposes PM5 for PTC (premature termination codon) variants only (PM5_PTC). This variant is an in-frame deletion, not a PTC. Classic same-residue missense PM5 does not apply to in-frame deletions. Details ▾Hide ▴
Evidence considered
- In-frame deletion
- not a PTC variant
- ENIGMA PM5_PTC only applies to PTC variants in exons where another proven pathogenic PTC exists
Sources
PM6 VCEPENIGMA BRCA2 specification marks PM6 as Not Applicable. Details ▾Hide ▴
No further detail was recorded.
PP2 VCEPENIGMA BRCA2 specification marks PP2 as Not Applicable. Details ▾Hide ▴
No further detail was recorded.
PP5 VCEPENIGMA BRCA2 specification marks PP5 as Not Applicable. ClinVar classification is Uncertain significance (1-star, single submitter), with 9 clinical laboratories reporting VUS and 1 reporting Likely benign. No expert panel review exists. Even under the global PP5/BP6 override (ClinVar 3-star EP → supporting), this does not qualify. Details ▾Hide ▴
No further detail was recorded.
BP2 VCEPENIGMA BRCA2 specification marks BP2 as Not Applicable. Details ▾Hide ▴
No further detail was recorded.
BP3 VCEPENIGMA BRCA2 specification marks BP3 as Not Applicable. Details ▾Hide ▴
No further detail was recorded.
BP6 VCEPENIGMA BRCA2 specification marks BP6 as Not Applicable. ClinVar classification is Uncertain significance (1-star, single submitter). No expert panel benign classification exists. Even under the global PP5/BP6 override, this does not qualify. Details ▾Hide ▴
No further detail was recorded.
PS5 N/APS5 is not defined in the ENIGMA BRCA2 specification (version 1.2). No gene-specific rules exist for this criterion. Details ▾Hide ▴
No further detail was recorded.
Identifiers
- Gene
- BRCA2
- Transcript
- NM_000059.3
- Coding (HGVS c.)
- NM_000059.3:c.5218_5223del
- Protein (HGVS p.)
- NP_000050.2:p.(Leu1740_Ser1741del)
- GRCh38
- chr13:32339571 ATTTAAG>A
- GRCh37
- chr13:32913708 ATTTAAG>A
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
10 / 1,609,336 alleles
AF 6.21e-06 · 0 homozygotes · FAF 4.35e-05
gnomAD v2.1
7 / 280,116 alleles
AF 2.5e-05 · 0 homozygotes · FAF 0.000106
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 6.2e-06 · 10 / 1,609,336 alleles · 0 hom · FAF 4.3e-05
| East Asian5 / 44,818 | 0.00011 |
| South Asian5 / 90,458 | 5.5e-05 |
0 alternate alleles recorded in 8 other groups: Remaining individuals, Admixed American, European (Finnish), Amish, Middle Eastern, Ashkenazi Jewish, African/African American, European (non-Finnish).
gnomAD v2.1
AF 2.5e-05 · 7 / 280,116 alleles · 0 hom · FAF 0.00011
| East Asian6 / 19,916 | 0.0003 |
| South Asian1 / 29,992 | 3.3e-05 |
0 alternate alleles recorded in 6 other groups: African/African American, Admixed American, Ashkenazi Jewish, European (Finnish), European (non-Finnish), Remaining individuals.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 6.21374e-06; MAF= 0.00062%, 10/1609336 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 0.000111562; MAF= 0.01116%, 5/44818 alleles, homozygotes = 0); grpmax FAF= 4.35e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 2.49896e-05; MAF= 0.00250%, 7/280116 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 0.000301265; MAF= 0.03013%, 6/19916 alleles, homozygotes = 0); grpmax FAF= 0.00010642.
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 This in-frame deletion (p.Leu1740_Ser1741del) lies outside the two ENIGMA-defined clinically important functional domains (BRCA2 PALB2 binding domain aa 10–40; BRCA2 DNA binding domain aa 2481–3186). SpliceAI predicts no splicing impact (max delta = 0.00). PP3 requires either location inside a clinically important domain with BayesDel ≥ 0.30, or SpliceAI ≥ 0.2. Neither condition is met. Details ▾Hide ▴
Evidence considered
- Variant at aa 1740–1741
- outside PALB2 binding (aa 10–40) and DNA binding (aa 2481–3186) domains
- SpliceAI max delta = 0.00
- no splicing impact predicted
- BayesDel not available (indel
- not SNV)
Sources
BP4 ENIGMA BP4 applies only to missense or in-frame variants located inside a clinically important functional domain with no predicted impact (BayesDel ≤ 0.18 and SpliceAI ≤ 0.1). This variant is at aa 1740–1741, outside the ENIGMA-defined clinically important domains (PALB2 binding aa 10–40; DNA binding aa 2481–3186). The domain location prerequisite is not satisfied. Details ▾Hide ▴
Evidence considered
- Variant outside clinically important functional domains
- SpliceAI max delta = 0.00
- no splicing impact
Sources
BP7 ENIGMA BP7 applies to (a) intronic/silent variants with mRNA assay evidence of no splicing impact (BP7_Strong RNA), or (b) silent variants inside a clinically important domain if BP4 is met (BP7_Supporting). This is an in-frame deletion, not a silent or intronic variant. No mRNA splicing assay data are available. Neither BP7 pathway applies. Details ▾Hide ▴
Evidence considered
- In-frame deletion
- not a silent or intronic variant
- No mRNA splicing assay data available
Still missing
- No mRNA assay data
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
5 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 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.Richards et al. 2015 ACMG/AMP standards and guidelines for sequence variant interpretation. This foundational guideline document does not discuss individual variants; NM_000059.3:c.5218_5223del was not identified in this paper.Does not name this variant
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PMID 30702160 ↗Germline variation in BRCA1/2 is highly ethnic-specific: Evidence from over 30,000 Chinese hereditary breast and ovarian cancer patients.Bhaskaran et al. 2019 study of germline BRCA1/2 variation in over 30,000 Chinese hereditary breast and ovarian cancer patients. Discusses ethnic-specific BRCA mutation spectra. NM_000059.3:c.5218_5223del was not identified in this paper.Does not name this variant
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PMID 36627197 ↗Profiling of the genetic features of Chinese patients with gastric cancer with HRD germline mutations in a large-scale retrospective study.Profiling of genetic features of Chinese gastric cancer patients with HRD germline mutations. Reports BRCA2 mutations in a gastric cancer context. NM_000059.3:c.5218_5223del was not identified in this paper.Does not name this variant
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PMID 18779604 ↗Performance of BRCA1/2 mutation prediction models in Asian Americans.Kurian et al. 2008 evaluation of BRCAPRO and Myriad II mutation prediction models in 200 Asian Americans versus 200 matched white individuals tested for BRCA1/2. Reports aggregate mutation counts by ethnicity. NM_000059.3:c.5218_5223del was not individually identified in this paper.Does not name this variant
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PMID 26187060 ↗Comprehensive spectrum of BRCA1 and BRCA2 deleterious mutations in breast cancer in Asian countries.Kwong et al. 2015 comprehensive review of BRCA1/2 deleterious mutation spectrum in breast cancer across 11 Asian countries. Catalogs 510 distinct mutations (268 BRCA1, 242 BRCA2) in Asian patients with breast cancer. NM_000059.3:c.5218_5223del was not identified among the reported mutations.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
10 / 1,609,336 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
9 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/?term=NM_000059.3%3Ac.5218_5223del
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/13-32913708-ATTTAAG-A?dataset…
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr13-32339571-ATTTAAG-A?data…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/13-32339571-ATTTAAG-A
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000059.3%3Ac.5218…
- OncoKB ↗www.oncokb.org/gene/BRCA2/L1740_S1741del
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=BRCA2+c.5218_5223del
- 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= 6.21374e-06; MAF= 0.00062%, 10/1609336 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 0.000111562; MAF= 0.01116%, 5/44818 alleles, homozygotes = 0); grpmax FAF= 4.35e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 2.49896e-05; MAF= 0.00250%, 7/280116 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 0.000301265; MAF= 0.03013%, 6/19916 alleles, homozygotes = 0); grpmax FAF= 0.00010642.
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Uncertain significance (9 clinical laboratories) and as Likely benign (1 clinical laboratory). (ClinVarID = 51824)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
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.