About BRCA2
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
BRCA2 c.4494T>A, p.(Gly1498=)
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: 3
Pathogenic criteria applied · 0
No pathogenic criterion marked as applied in the recorded assessment.
Benign criteria applied · 3
BS1Supporting
BS1 · supporting
BS1_Supporting is met. ENIGMA BS1_Supporting requires FAF > 0.002% (FAF > 0.00002) and ≤ 0.01% (FAF ≤ 0.0001) in gnomAD non-cancer populations. gnomAD v4.1 grpmax FAF = 3.34e-05 (0.0033%) exceeds the 0.002% threshold and is ≤ 0.01%. The gnomAD v2.1 FAF (1.69e-05, 0.0017%) does not meet the threshold, but v4.1 serves as a more comprehensive non-cancer population dataset. Note: ENIGMA specification references gnomAD v3.1; v4.1 (the successor) is used here as the current best available non-cancer population frequency resource.
BP1Strong
BP1 · strong
BP1_Strong is met. ENIGMA BP1_Strong applies to silent substitutions outside a (potentially) clinically important functional domain with no splicing predicted (SpliceAI ≤0.1). c.4494T>A is a synonymous variant (p.Gly1498=) at amino acid position 1498, which lies outside both BRCA2 clinically important functional domains (PALB2 binding: aa 10-40; DNA binding: aa 2481-3186). SpliceAI max delta = 0.00. All conditions for BP1_Strong are satisfied.
BP6Supporting
BP6 · supporting
Expert panel Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) classified as Likely benign.
Recorded classification: Likely benign
ENIGMA BRCA1/BRCA2 Specification v1.2.0 Table 3 classification framework applied. One Strong (Benign) criterion (BP1_Strong) and one Supporting (Benign) criterion (BS1_Supporting) are met, satisfying the ENIGMA Likely Benign combination rule. ENIGMA point system yields -5 points (BP1_Strong = -4, BS1_Supporting = -1), falling in the Likely Benign range (-6 to -2). No pathogenic 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
52 / 1,613,516 alleles
gnomAD v4.1: 52 / 1,613,516 alleles. Recorded AF 3.22278e-05. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.99692e-05; MAF= 0.00200%, 5/250386 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 4.42642e-05; MAF= 0.00443%, 5/112958 alleles, homozygotes = 0); grpmax FAF= 1.694e-05.
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
13 reported laboratory submissions
11 Likely benign · 1 Likely Benign · 1 Benign.
Functional evidence
Statement recorded
OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
No matching record reported
This variant has not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under ClinGen BRCA2 VCEP v1.2.0, with the data and sources behind each one.
26 criteria with recorded statuses: 3 met · 10 not met · 2 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
NM_000059.4:c.4494T>A (p.Gly1498=) is a synonymous variant in BRCA2 exon 11.
BP1_Strong is met: the variant is a silent substitution outside the clinically important functional domains (aa 10-40 and 2481-3186) with no predicted splicing impact (SpliceAI max delta=0.00).
BS1_Supporting is met: gnomAD v4.1 filter allele frequency is 3.34e-05 (0.0033%), exceeding the 0.002% threshold for BS1_Supporting under ENIGMA rules.
PVS1, PS3, PM2, PM5, PP3, PP4, BA1, BS3, BS4, and BP5 are not met or not applicable. The variant is present in gnomAD, lacks functional evidence of pathogenicity, and has no segregation or case-control data.
ClinVar expert panel (ENIGMA) classifies this variant as Likely Benign (ClinVar ID: 184407), consistent with the criteria assessment.
Applying ENIGMA Table 3 point system: BP1_Strong = -4 points, BS1_Supporting = -1 point, total = -5 points, which falls in the Likely Benign range (-6 to -2). The combination of one Strong (Benign) and one Supporting (Benign) criterion satisfies the ENIGMA Likely Benign classification rule.
Exploratory evidence suggests c.4494T>A exhibits normal splicing in a minigene assay (PMID:28608497), which, if verified, would add BP7_Strong (RNA), further strengthening the benign classification.
No criteria match.
Met · 3
BS1 SupportingBS1_Supporting is met. ENIGMA BS1_Supporting requires FAF > 0.002% (FAF > 0.00002) and ≤ 0.01% (FAF ≤ 0.0001) in gnomAD non-cancer populations. gnomAD v4.1 grpmax FAF = 3.34e-05 (0.0033%) exceeds the 0.002% threshold and is ≤ 0.01%. The gnomAD v2.1 FAF (1.69e-05, 0.0017%) does not meet the threshold, but v4.1 serves as a more comprehensive non-cancer population dataset. Note: ENIGMA specification references gnomAD v3.1; v4.1 (the successor) is used here as the current best available non-cancer population frequency resource. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 grpmax FAF=3.34e-05 (0.0033%) > 0.002% threshold for BS1_Supporting
- gnomAD v2.1 grpmax FAF=1.69e-05 (0.0017%) below threshold
Still missing
- ENIGMA specification references gnomAD v3.1
- v4.1 used as proxy. Confirm v3.1 FAF if available.
Sources
BP1 StrongBP1_Strong is met. ENIGMA BP1_Strong applies to silent substitutions outside a (potentially) clinically important functional domain with no splicing predicted (SpliceAI ≤0.1). c.4494T>A is a synonymous variant (p.Gly1498=) at amino acid position 1498, which lies outside both BRCA2 clinically important functional domains (PALB2 binding: aa 10-40; DNA binding: aa 2481-3186). SpliceAI max delta = 0.00. All conditions for BP1_Strong are satisfied. Details ▾Hide ▴
Evidence considered
- Synonymous variant p.(Gly1498=) at position 1498
- Position outside functional domains (aa 10-40 and 2481-3186)
- SpliceAI max delta = 0.00
Sources
Not met · 10 · evaluated, threshold not reached
PS3 PS3 is not met. No well-established functional assay demonstrates a damaging effect. ENIGMA Specifications Table 9 (curated functional assay results) has no entry for c.4494T>A. No published study reports a gain-of-function or splicing abnormality supporting pathogenicity. Details ▾Hide ▴
Evidence considered
- Absent from ENIGMA Table 9 functional assay catalogue
- No published evidence of damaging functional effect
Still missing
- PMID:28608497 (Fraile-Bethencourt et al. 2017) is reported to have tested c.4494T>A in a minigene assay but full text was not available for verification in this adjudication
Sources
vcep_specifications_table9_v1_2_2024_11_18257418682646702528492532
PS4 PS4 is not met. No case-control study demonstrates statistically significant enrichment of c.4494T>A in affected individuals versus controls. The variant is present in gnomAD population databases at low frequency, inconsistent with a high-penetrance pathogenic variant. No published proband series specific to this variant was identified. Details ▾Hide ▴
Evidence considered
- Present in gnomAD v2.1 (5/250
- 386 alleles
- FAF=1.69e-05)
- Present in gnomAD v4.1 (52/1
- 613
- 516 alleles
- FAF=3.34e-05)
- No case enrichment data in published literature
Still missing
- No formal case-control odds ratio available
Sources
PM2 PM2 is not met. ENIGMA PM2_Supporting requires absence from gnomAD v2.1 (non-cancer, exome only subset) and gnomAD v3.1 (non-cancer). c.4494T>A is present in gnomAD v2.1 with 5 alleles (FAF=1.69e-05) and in gnomAD v4.1 with 52 alleles (FAF=3.34e-05). The variant is observed in outbred populations, therefore PM2 cannot be applied. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: 5/250
- 386 exome alleles
- grpmax FAF=1.69e-05
- gnomAD v4.1: 52/1
- 613
- 516 alleles
- grpmax FAF=3.34e-05
Sources
PP1 PP1 is not met. No co-segregation analysis in affected family members is available for c.4494T>A. No quantitative co-segregation LR has been published for this variant. Details ▾Hide ▴
Evidence considered
- No published co-segregation data
Still missing
- No family-based segregation analysis available
PP3 PP3 is not met. ENIGMA PP3 requires either (a) missense/in-frame variant inside a clinically important functional domain with BayesDel no-AF score ≥0.30, or (b) SpliceAI ≥0.2 for silent/missense/in-frame variants. c.4494T>A is a synonymous variant with SpliceAI max delta = 0.00, located outside the clinically important functional domains (aa 10-40 and aa 2481-3186). BayesDel score is not available. Neither condition is satisfied. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.00
- Variant at position 1498
- outside functional domains (aa 10-40
- 2481-3186)
- BayesDel score not available (null)
Sources
PP4 PP4 is not met. ENIGMA PP4 is applied using the clinical-history likelihood ratio from Li et al. 2020 (PMID:31853058). The variant-level clinical history LR spreadsheet has no entry for NM_000059.4:c.4494T>A, so no LR is available to support pathogenicity from personal/family history data. Details ▾Hide ▴
Evidence considered
- Absent from Li et al. 2020 BRCA2 clinical history LR table
Still missing
- No clinical history LR available for this variant
Sources
vcep_pmid_31853058_brca2_clinical_history_lr31853058
BA1 BA1 is not met. ENIGMA BA1 requires filter allele frequency (FAF) above 0.1% (FAF > 0.001) in gnomAD v2.1 (non-cancer, exome only subset) and/or gnomAD v3.1 (non-cancer), non-founder populations. gnomAD v2.1 grpmax FAF = 1.69e-05 (0.0017%) and gnomAD v4.1 grpmax FAF = 3.34e-05 (0.0033%), both well below the 0.1% threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 grpmax FAF=1.69e-05 (<0.001)
- gnomAD v4.1 grpmax FAF=3.34e-05 (<0.001)
Sources
BS2 BS2 is not met. ENIGMA BS2 requires proband-level data demonstrating absence of Fanconi Anemia phenotype with sufficient points per Specifications Table 8. No proband phenotype data specific to c.4494T>A are available for BS2 adjudication. Details ▾Hide ▴
Evidence considered
- No proband phenotype data available for BS2 assessment
Still missing
- Proband-level phenotype data not available
BS4 BS4 is not met. ENIGMA BS4 requires quantitative co-segregation analysis demonstrating lack of segregation with disease (LR thresholds per Appendix I). No segregation data for c.4494T>A are available. Details ▾Hide ▴
Evidence considered
- No published segregation analysis for this variant
Still missing
- No family-based lack-of-segregation data
BP5 BP5 is not met. ENIGMA BP5 is applied using the clinical-history likelihood ratio from Li et al. 2020 (PMID:31853058). The variant-level clinical history LR spreadsheet has no entry for NM_000059.4:c.4494T>A, so no LR is available to support benignity from personal/family history data. Details ▾Hide ▴
Evidence considered
- Absent from Li et al. 2020 BRCA2 clinical history LR table
Still missing
- No clinical history LR available for this variant
Sources
vcep_pmid_31853058_brca2_clinical_history_lr31853058
Not assessed · 2 · no assessment recorded
BS3 BS3 is not assessed. ENIGMA BS3 requires well-established functional studies showing no damaging effect on protein function, with code assignments per Specifications Table 9. Table 9 has no entry for c.4494T>A. Exploratory evidence suggests PMID:28608497 (Fraile-Bethencourt et al. 2017) tested c.4494T>A in a minigene splicing assay and observed normal splicing; this would map to BP7 (RNA) rather than BS3 under ENIGMA rules. Full text of PMID:28608497 was not available for verification in this adjudication. Details ▾Hide ▴
Evidence considered
- Absent from ENIGMA Table 9 functional assay catalogue
- Exploratory result references PMID:28608497 for normal splicing (not verified)
Still missing
- PMID:28608497 full text not verified
- if normal splicing confirmed
- would support BP7 (RNA) rather than BS3
Sources
vcep_specifications_table9_v1_2_2024_11_182574186826467025
BP7 BP7 is not assessed. ENIGMA BP7_Strong (RNA) would apply if well-established mRNA assay data demonstrate no aberrant splicing for this silent variant outside the functional domain. Exploratory evidence indicates PMID:28608497 (Fraile-Bethencourt et al. 2017) tested c.4494T>A via minigene assay and observed normal splicing, which would support BP7_Strong (RNA) if verified. ENIGMA BP7_Supporting is not applicable because the variant is outside the clinically important functional domain. Full text of PMID:28608497 was not available for verification. Details ▾Hide ▴
Evidence considered
- Exploratory result references PMID:28608497 for normal splicing (not verified)
- Silent variant outside functional domain
- eligible for BP7_Strong (RNA) if normal splicing confirmed
Still missing
- PMID:28608497 full text not verified
- if normal splicing confirmed
- BP7_Strong (RNA) would be met
Not applicable · 11· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/APVS1 is not applicable. NM_000059.4:c.4494T>A is a synonymous variant (p.Gly1498=) that does not fall into any null-variant bucket (nonsense, frameshift, canonical ±1,2 splice). SpliceAI max delta = 0.00 confirms no cryptic splice defect. Not eligible for PVS1 or PVS1 (RNA) under ENIGMA v1.2.0. Details ▾Hide ▴
Evidence considered
- Synonymous variant (p.Gly1498=)
- SpliceAI max delta score = 0.00
- PVS1 variant assessment confirms 'other' bucket
- not a null variant
Sources
pvs1_variant_assessmentspliceai ↗
PS1 N/APS1 is not applicable. ENIGMA PS1 applies to predicted missense substitutions with a previously classified pathogenic variant at the same residue, or to exonic/intronic variants with the same predicted splicing impact as a known pathogenic variant. c.4494T>A is a synonymous variant with no predicted splice impact (SpliceAI=0.00) and no pathogenic comparator at this residue. Details ▾Hide ▴
Evidence considered
- Synonymous variant
- no amino acid change
- SpliceAI max delta = 0.00
Sources
PS2 VCEPSkipped per adjudication instruction. No de novo data available for this variant. Details ▾Hide ▴
No further detail was recorded.
PM1 VCEPPM1 is not applicable per ENIGMA BRCA1/BRCA2 Expert Panel Specification v1.2.0, which explicitly marks PM1 as Not Applicable. Details ▾Hide ▴
PM5 N/APM5 is not applicable. ENIGMA repurposes PM5 exclusively for protein termination codon (PTC) variants where a different proven pathogenic PTC has been seen in the same exon (PM5_PTC). c.4494T>A is a synonymous variant, not a PTC. Classic same-residue missense PM5 is also not applicable as this variant does not alter the amino acid. Details ▾Hide ▴
Evidence considered
- Synonymous variant
- not a PTC
- PM5 candidates report confirms not eligible for classic or PTC PM5
Sources
pm5_candidatesvcep_specifications_table4_v1_2_2024_11_18
PM6 VCEPSkipped per adjudication instruction. No de novo data for this variant. Details ▾Hide ▴
No further detail was recorded.
PP2 VCEPPP2 is not applicable per ENIGMA BRCA1/BRCA2 Expert Panel Specification v1.2.0, which explicitly marks PP2 as Not Applicable. Details ▾Hide ▴
PP5 VCEPPP5 is not applicable per ENIGMA BRCA1/BRCA2 Expert Panel Specification v1.2.0, which explicitly marks PP5 as Not Applicable. Details ▾Hide ▴
BP2 VCEPBP2 is not applicable per ENIGMA BRCA1/BRCA2 Expert Panel Specification v1.2.0, which explicitly marks BP2 as Not Applicable. Details ▾Hide ▴
BP4 N/ABP4 is not applicable. ENIGMA BP4 applies to (a) missense/in-frame variants inside a clinically important functional domain with no predicted impact, (b) silent variants inside a clinically important functional domain with SpliceAI ≤0.1, or (c) intronic variants outside native splice sites with SpliceAI ≤0.1. c.4494T>A is a silent variant at position 1498, which is outside both clinically important functional domains (aa 10-40 and aa 2481-3186). It is not intronic. None of the BP4 conditions are satisfied. Details ▾Hide ▴
Evidence considered
- Silent variant outside functional domains
- Position 1498 not in aa 10-40 or aa 2481-3186
Sources
PS5 N/APS5 is not applicable. c.4494T>A is a synonymous variant with no amino acid change. There is no alternate pathogenic nucleotide change at c.4494 to support PS5. Details ▾Hide ▴
Evidence considered
- Synonymous variant
- no alternate pathogenic change at this position
Identifiers
- Gene
- BRCA2
- Transcript
- NM_000059.4
- Coding (HGVS c.)
- NM_000059.4:c.4494T>A
- Protein (HGVS p.)
- NP_000050.3:p.(Gly1498=)
- GRCh38
- chr13:32338849 T>A
- GRCh37
- chr13:32912986 T>A
- ClinVar
- 2713314, 184407
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
52 / 1,613,516 alleles
AF 3.22e-05 · 0 homozygotes · FAF 3.34e-05
gnomAD v2.1
5 / 250,386 alleles
AF 2e-05 · 0 homozygotes · FAF 1.69e-05
gnomAD-Canada v1.0
0 / 0 alleles
AF 0 · 0 homozygotes · FAF 0
By genetic ancestry
gnomAD v4.1
AF 3.2e-05 · 52 / 1,613,516 alleles · 0 hom · FAF 3.3e-05
| European (non-Finnish)51 / 1,179,602 | 4.3e-05 |
| African/African American1 / 74,922 | 1.3e-05 |
0 alternate alleles recorded in 8 other groups: Remaining individuals, Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish.
gnomAD v2.1
AF 2e-05 · 5 / 250,386 alleles · 0 hom · FAF 1.7e-05
| European (non-Finnish)5 / 112,958 | 4.4e-05 |
0 alternate alleles recorded in 7 other groups: African/African American, Admixed American, Ashkenazi Jewish, East Asian, European (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= 3.22278e-05; MAF= 0.00322%, 52/1613516 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 4.32349e-05; MAF= 0.00432%, 51/1179602 alleles, homozygotes = 0); grpmax FAF= 3.342e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.99692e-05; MAF= 0.00200%, 5/250386 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 4.42642e-05; MAF= 0.00443%, 5/112958 alleles, homozygotes = 0); grpmax FAF= 1.694e-05.
SpliceAI and Pangolin
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
PP3 PP3 is not met. ENIGMA PP3 requires either (a) missense/in-frame variant inside a clinically important functional domain with BayesDel no-AF score ≥0.30, or (b) SpliceAI ≥0.2 for silent/missense/in-frame variants. c.4494T>A is a synonymous variant with SpliceAI max delta = 0.00, located outside the clinically important functional domains (aa 10-40 and aa 2481-3186). BayesDel score is not available. Neither condition is satisfied. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.00
- Variant at position 1498
- outside functional domains (aa 10-40
- 2481-3186)
- BayesDel score not available (null)
Sources
BP7 BP7 is not assessed. ENIGMA BP7_Strong (RNA) would apply if well-established mRNA assay data demonstrate no aberrant splicing for this silent variant outside the functional domain. Exploratory evidence indicates PMID:28608497 (Fraile-Bethencourt et al. 2017) tested c.4494T>A via minigene assay and observed normal splicing, which would support BP7_Strong (RNA) if verified. ENIGMA BP7_Supporting is not applicable because the variant is outside the clinically important functional domain. Full text of PMID:28608497 was not available for verification. Details ▾Hide ▴
Evidence considered
- Exploratory result references PMID:28608497 for normal splicing (not verified)
- Silent variant outside functional domain
- eligible for BP7_Strong (RNA) if normal splicing confirmed
Still missing
- PMID:28608497 full text not verified
- if normal splicing confirmed
- BP7_Strong (RNA) would be met
BP4 N/ABP4 is not applicable. ENIGMA BP4 applies to (a) missense/in-frame variants inside a clinically important functional domain with no predicted impact, (b) silent variants inside a clinically important functional domain with SpliceAI ≤0.1, or (c) intronic variants outside native splice sites with SpliceAI ≤0.1. c.4494T>A is a silent variant at position 1498, which is outside both clinically important functional domains (aa 10-40 and aa 2481-3186). It is not intronic. None of the BP4 conditions are satisfied. Details ▾Hide ▴
Evidence considered
- Silent variant outside functional domains
- Position 1498 not in aa 10-40 or aa 2481-3186
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
9 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
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PMID 23918944 ↗Tamoxifen and risk of contralateral breast cancer for BRCA1 and BRCA2 mutation carriers.No paper-specific finding is recorded.
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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.
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PMID 26467025 ↗A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.No paper-specific finding is recorded.
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PMID 12692171 ↗American Society of Clinical Oncology policy statement update: genetic testing for cancer susceptibility.American Society of Clinical Oncology · 2003No paper-specific finding is recorded.
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PMID 15604628 ↗Genetic cancer risk assessment and counseling: recommendations of the national society of genetic counselors.Trepanier A et al. · 2004No paper-specific finding is recorded.
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PMID 17392385 ↗American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography.Saslow D et al. · 2007No paper-specific finding is recorded.
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PMID 17508274 ↗Risk assessment and genetic counseling for hereditary breast and ovarian cancer: recommendations of the National Society of Genetic Counselors.Berliner JL et al. · 2007No paper-specific finding is recorded.
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PMID 18163131 ↗The emerging landscape of breast cancer susceptibility.Stratton MR et al. · 2008No 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
52 / 1,613,516 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
11 Likely benign · 1 Likely Benign · 1 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/184407/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/13-32912986-T-A?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr13-32338849-T-A?dataset=gn…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000059.4%3Ac.4494…
- OncoKB ↗www.oncokb.org/gene/BRCA2/G1498=
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=BRCA2+c.4494T%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= 3.22278e-05; MAF= 0.00322%, 52/1613516 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 4.32349e-05; MAF= 0.00432%, 51/1179602 alleles, homozygotes = 0); grpmax FAF= 3.342e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.99692e-05; MAF= 0.00200%, 5/250386 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 4.42642e-05; MAF= 0.00443%, 5/112958 alleles, homozygotes = 0); grpmax FAF= 1.694e-05.
ClinVar
This variant has been reported in ClinVar as Likely benign (11 clinical laboratories) and as Likely Benign (1 clinical laboratory) and as Benign (1 clinical laboratory) and as Likely benign by Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) (expert panel). (ClinVarID = 184407)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
Functional
OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.
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.