About BRCA2
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
BRCA2 c.3417G>A, p.(Lys1139=)
Classification
Likely benign
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is likely benign. Select a step to read what it means.
Likely benign.A likely benign classification under the recorded framework.
In plain language
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.
LYFE Sciences is an AI system, and it can make mistakes.
Criteria may be applied incorrectly, sources may be misread, and a
confident-looking classification can still be wrong.
Double-check every criterion and its underlying evidence
before relying on any call.
01The reasoning
How it was classified
The recorded framework is ClinGen BRCA2 VCEP v1.2.0. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.
Recorded applied criteria
The applied criteria and their strengths are shown as assessed under the stated framework.
Pathogenic evidence criteria: 0
Benign evidence criteria: 2
Pathogenic criteria applied · 0
No pathogenic criterion marked as applied in the recorded assessment.
Benign criteria applied · 2
BP1Strong
BP1 · strong
BP1_Strong applies under ENIGMA v1.2: c.3417G>A is a silent substitution (p.Lys1139=) located at residue 1139, which is outside both BRCA2 clinically important functional domains (PALB2 binding domain aa 10-40 and DNA binding domain aa 2481-3186). SpliceAI predicts no splicing impact (max delta = 0.00, ≤ 0.1). Both 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 v1.2 Table 3 rules applied. Zero pathogenic criteria met. BP1_Strong (strong benign) plus BP6 (supporting benign) satisfies the Likely Benign combination rule: Strong (Benign) count=1 + Supporting (Benign) count=1.
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
162 / 1,613,842 alleles
gnomAD v4.1: 162 / 1,613,842 alleles. Recorded AF 0.000100382. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000159399; MAF= 0.01594%, 40/250942 alleles, homozygotes = 0) and has highest observed frequency in the Ashkenazi Jewish population (AF= 0.00357427; MAF= 0.35743%, 36/10072 alleles, homozygotes = 0); grpmax FAF= 2.93e-06.
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
12 reported laboratory submissions
8 Likely benign · 3 Benign · 1 Likely 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.
29 criteria with recorded statuses: 2 met · 5 not met · 8 not assessed · 14 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_000059.4:c.3417G>A (p.Lys1139=) is a synonymous substitution in BRCA2 exon 11, located outside both clinically important functional domains defined by ENIGMA (aa 10-40 PALB2 binding and aa 2481-3186 DNA binding).
BP1_Strong is met: silent substitution outside a clinically important functional domain with no predicted splicing impact (SpliceAI max delta = 0.00).
The variant is present in gnomAD v2.1 (40/250,942 alleles, AF=0.000159) and v4.1 (162/1,613,842 alleles, AF=0.000100), with highest frequency in the Ashkenazi Jewish population (AF=0.00357), consistent with a founder effect. The grpmax filter allele frequency (FAF=2.93e-06 v2.1, FAF=1.88e-05 v4.1) does not meet ENIGMA BS1 thresholds.
The variant has been classified as Likely benign by the ENIGMA expert panel in ClinVar (Variation ID 135796, 3-star review status), with 8 clinical laboratories reporting Likely benign, 3 reporting Benign, and 1 reporting Likely Benign.
No variant-specific functional assay data, segregation analysis, case-control data, or clinical-history likelihood ratios were identified for this variant in the ENIGMA curated datasets (Table 9, HUMU, clinical_history_LR, ST7) or in the reviewed literature.
No publication among the 8 PMIDs reviewed (20104584, 25741868, 23918944, 23788249, 17392385, 18163131, 20301425, 28492532) contained a specific mention of NM_000059.4:c.3417G>A.
No criteria match.
Met · 2
BP1 StrongBP1_Strong applies under ENIGMA v1.2: c.3417G>A is a silent substitution (p.Lys1139=) located at residue 1139, which is outside both BRCA2 clinically important functional domains (PALB2 binding domain aa 10-40 and DNA binding domain aa 2481-3186). SpliceAI predicts no splicing impact (max delta = 0.00, ≤ 0.1). Both conditions for BP1_Strong are satisfied. Details ▾Hide ▴
Evidence considered
- Silent substitution (synonymous) at codon 1139.
- K1139 is outside clinically important functional domains (PALB2 binding: aa 10-40
- DNA binding: aa 2481-3186).
- SpliceAI max delta = 0.00 (no predicted splice effect).
- ENIGMA v1.2 BP1_Strong rule: silent variant outside functional domain with SpliceAI ≤ 0.1.
Sources
Not met · 5 · evaluated, threshold not reached
PM2 PM2_Supporting under ENIGMA requires absence from gnomAD v2.1 (non-cancer, exome only) and gnomAD v3.1 (non-cancer) outbred populations. This variant is present in gnomAD v2.1 at AF=0.000159 (40/250,942 alleles) and in gnomAD v4.1 at AF=0.000100 (162/1,613,842 alleles), so the absence criterion is not satisfied. Details ▾Hide ▴
Evidence considered
- Present in gnomAD v2.1: 40/250
- 942 alleles (AF=0.000159).
- Present in gnomAD v4.1: 162/1
- 613
- 842 alleles (AF=0.000100).
- Highest frequency in Ashkenazi Jewish population: 36/10
- 072 (AF=0.00357).
Sources
PP3 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 delta ≥ 0.20 for silent/missense/intronic variants. This variant is synonymous, located outside BRCA2 clinically important functional domains (aa 10-40 and aa 2481-3186), and SpliceAI max delta is 0.00. Neither pathway is satisfied. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.00 (no predicted splice impact).
- K1139 is outside BRCA2 clinically important functional domains (PALB2 binding: aa 10-40
- DNA binding: aa 2481-3186).
Sources
PP5 The ENIGMA expert panel has classified this variant as Likely benign in ClinVar (Variation ID 135796, review status: reviewed by expert panel). PP5 is a pathogenic criterion requiring a reputable source to have classified the variant as pathogenic; the expert panel classification is benign-direction, not pathogenic. Details ▾Hide ▴
Evidence considered
- ClinVar expert panel (ENIGMA) classification: Likely benign.
- 8 clinical laboratories: Likely benign
- 3: Benign
- 1: Likely Benign.
Sources
BA1 ENIGMA BA1 (Stand Alone benign) requires filter allele frequency (FAF) > 0.001 (0.1%) in gnomAD non-founder populations. The grpmax FAF is 2.93e-06 (v2.1) and 1.88e-05 (v4.1), both well below the BA1 threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 grpmax FAF = 2.93e-06 (far below BA1 threshold of 0.001).
- gnomAD v4.1 grpmax FAF = 1.88e-05 (far below BA1 threshold of 0.001).
Sources
BS1 ENIGMA BS1_Strong requires FAF > 0.0001 and BS1_Supporting requires FAF > 0.00002 in gnomAD non-founder populations. The grpmax FAF is 2.93e-06 (gnomAD v2.1) and 1.88e-05 (gnomAD v4.1), both below the BS1_Supporting threshold of 0.00002. The elevated Ashkenazi Jewish frequency (AF=0.00357) is attributable to a known founder effect and is excluded by the FAF adjustment. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 grpmax FAF = 2.93e-06 (< BS1_Supporting threshold of 0.00002).
- gnomAD v4.1 grpmax FAF = 1.88e-05 (< BS1_Supporting threshold of 0.00002).
- Ashkenazi Jewish frequency (AF=0.0036) is characterized as a founder effect
- excluded from FAF calculation.
Sources
Not assessed · 8 · no assessment recorded
PS3 No variant-specific functional assay data were identified in the ENIGMA curated functional assay table (Specifications Table 9), the HUMU multifactorial dataset, or any reviewed publication. The variant is not listed in any calibrated BRCA2 functional study. Details ▾Hide ▴
Evidence considered
- Absent from ENIGMA Table 9 (curated PS3/BS3 assignments).
- Not found in HUMU SuppT4 functional assay data.
Still missing
- No functional assay data available for this specific variant.
Sources
vcep_specifications_table9_v1_2_2024_11_18vcep_humu_40_1557_s001
PS4 No case-control study with variant-specific odds ratio and p-value meeting ENIGMA PS4 thresholds (p ≤ 0.05, OR ≥ 4, lower CI excludes 2.0) was identified. The WECARE study (PMID:20104584) compared aggregated VUS groups but did not provide variant-level case-control data for c.3417G>A. Details ▾Hide ▴
Evidence considered
- WECARE study aggregated synonymous BRCA2 VUS showed no statistically significant risk of contralateral breast cancer (RR ~1.0)
- but variant-level data were not reported.
Still missing
- No variant-specific case-control data available.
Sources
PP1 No co-segregation data or LR analysis meeting ENIGMA PP1 thresholds (LR ≥ 2.08) were identified for this variant. No variant-specific segregation analysis was found in the reviewed publications or VCEP reference datasets. Details ▾Hide ▴
Evidence considered
- No variant-specific co-segregation analysis identified.
Still missing
- No segregation data available for this specific variant.
PP4 No variant-specific clinical-history likelihood ratio meeting ENIGMA PP4 thresholds (LR ≥ 2.08) was identified. The variant was not found in the Li et al. 2020 (PMID:31853058) BRCA2 clinical_history_LR spreadsheet. Details ▾Hide ▴
Evidence considered
- Not listed in Li et al. 2020 BRCA2 clinical-history LR table.
Still missing
- No variant-specific clinical history LR data available.
Sources
vcep_pmid_31853058_brca2_clinical_history_lr
BS2 ENIGMA BS2 requires assessment of observed homozygotes or compound heterozygotes for absence of Fanconi Anemia phenotype, using a points-based system (Specifications Table 8). No variant-specific proband data with FA phenotype assessment were identified. gnomAD v2.1 reports 0 homozygotes out of 250,942 alleles. Details ▾Hide ▴
Evidence considered
- No homozygotes observed in gnomAD v2.1 (0/250
- 942).
- No FA phenotype data available for BS2 point assignment.
Still missing
- No proband-level FA phenotype data available for BS2 point assignment.
Sources
BS3 No variant-specific functional assay data showing no damaging effect on protein function were identified. The variant is absent from ENIGMA Table 9 (curated BS3 assignments) and the HUMU SuppT4 functional assay dataset. No publication with variant-specific functional data was found. Details ▾Hide ▴
Evidence considered
- Absent from ENIGMA Table 9 (curated PS3/BS3 assignments).
- Not found in HUMU SuppT4 functional assay data.
Still missing
- No functional assay data available for this specific variant.
Sources
vcep_specifications_table9_v1_2_2024_11_18vcep_humu_40_1557_s001
BS4 No variant-specific lack-of-segregation LR analysis meeting ENIGMA BS4 thresholds (LR ≤ 0.48) was identified. The variant was not found in the ENIGMA Supplementary Table ST7 reference set or the HUMU multifactorial dataset. Details ▾Hide ▴
Evidence considered
- Not found in ST7 reference set.
- Not found in HUMU SuppT1 multifactorial data.
Still missing
- No segregation data available for this specific variant.
Sources
vcep_supplementarytables_v1_2_2024_11_18vcep_humu_40_1557_s001
BP5 No variant-specific clinical-history likelihood ratio meeting ENIGMA BP5 thresholds (LR ≤ 0.48) was identified. The variant was not found in the Li et al. 2020 (PMID:31853058) BRCA2 clinical_history_LR spreadsheet. Details ▾Hide ▴
Evidence considered
- Not listed in Li et al. 2020 BRCA2 clinical-history LR table.
Still missing
- No variant-specific clinical history LR data available.
Sources
vcep_pmid_31853058_brca2_clinical_history_lr
Not applicable · 14· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANM_000059.4:c.3417G>A is a synonymous substitution (NP_000050.3:p.Lys1139=) and does not fall into any ENIGMA PVS1 null-variant category (nonsense, frameshift, canonical splice site, initiation codon, or exon deletion). Details ▾Hide ▴
Evidence considered
- Synonymous variant with no predicted effect on protein sequence
- SpliceAI max delta = 0.00 confirms no cryptic splice impact.
Sources
pvs1_variant_assessment
PS1 N/APS1 under ENIGMA v1.2 applies to missense substitutions with a previously classified pathogenic comparator at the same residue, or to splice-impact variants with same predicted splicing outcome as a known pathogenic variant. This variant is synonymous with SpliceAI delta = 0.00, so neither pathway applies. Details ▾Hide ▴
Evidence considered
- Synonymous substitution with no predicted splice impact.
PS2 VCEPENIGMA v1.2 explicitly designates PS2 as not applicable for this VCEP. Details ▾Hide ▴
PM1 VCEPENIGMA v1.2 designates PM1 as not applicable; domain-level analysis is captured through the bioinformatic code application flowchart (PP3/BP4) instead. Details ▾Hide ▴
Evidence considered
- VCEP specification states PM1 is not applicable
- considered as component of bioinformatic analysis (PP3/BP4).
Sources
PM3 N/ASkipped per user directive: not applicable for this variant type (synonymous substitution in BRCA2 without Fanconi Anemia phenotype data). Details ▾Hide ▴
Evidence considered
- Trivially not applicable
- skipped by user directive.
PM4 VCEPSkipped per user directive: NM_000059.4:c.3417G>A is a substitution, not an in-frame deletion/insertion or stop-loss variant. Details ▾Hide ▴
Evidence considered
- Trivially not applicable for a single-nucleotide substitution
- skipped by user directive.
PM5 N/AENIGMA PM5 is repurposed as PM5_PTC for protein termination codon variants only. This variant is synonymous (K1139=), not a PTC, and the pm5_candidates assessment confirmed PM5 is not applicable via either classic same-residue missense or PTC pathways. Details ▾Hide ▴
Evidence considered
- Synonymous variant
- not a PTC. PM5_PTC exon-based rules do not apply.
Sources
pm5_candidates
PM6 VCEPENIGMA v1.2 explicitly designates PM6 as not applicable for this VCEP. Details ▾Hide ▴
PP2 VCEPENIGMA v1.2 explicitly designates PP2 as not applicable for this VCEP. Details ▾Hide ▴
BP2 VCEPENIGMA v1.2 explicitly designates BP2 as not applicable for this VCEP. Details ▾Hide ▴
BP3 VCEPENIGMA v1.2 designates BP3 as not applicable; captured by bioinformatic tool prediction and domain analysis. Details ▾Hide ▴
BP4 N/AENIGMA BP4 applies only to missense, in-frame, or silent variants inside a clinically important functional domain with no predicted impact. Residue K1139 is outside both BRCA2 clinically important functional domains (PALB2 binding aa 10-40 and DNA binding aa 2481-3186), so BP4 does not apply. Details ▾Hide ▴
Evidence considered
- K1139 is outside clinically important functional domains.
- ENIGMA BP4 rule requires variant to be inside a functional domain.
Sources
BP7 N/AENIGMA BP7_Supporting requires a silent variant inside a clinically important functional domain with BP4 met. BP7_Strong (RNA) requires well-established mRNA assay data showing no damaging effect. K1139 is outside the functional domains, BP4 is not met, and no variant-specific RNA assay data were identified. Details ▾Hide ▴
Evidence considered
- K1139 is outside clinically important functional domains
- BP4 prerequisite not met.
- No variant-specific mRNA assay data available for BP7_Strong(RNA).
Sources
PS5 N/APS5 is not part of the ENIGMA BRCA2 VCEP v1.2 framework; this criterion is not defined in the CSPEC ruleset. Details ▾Hide ▴
Identifiers
- Gene
- BRCA2
- Transcript
- NM_000059.4
- Coding (HGVS c.)
- NM_000059.4:c.3417G>A
- Protein (HGVS p.)
- NP_000050.3:p.(Lys1139=)
- GRCh38
- chr13:32337772 G>A
- GRCh37
- chr13:32911909 G>A
- ClinVar
- 135796
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
162 / 1,613,842 alleles
AF 0.0001 · 0 homozygotes · FAF 1.88e-05
gnomAD v2.1
40 / 250,942 alleles
AF 0.000159 · 0 homozygotes · FAF 2.93e-06
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 0.0001 · 162 / 1,613,842 alleles · 0 hom · FAF 1.9e-05
| Ashkenazi Jewish122 / 29,594 | 0.0041 |
| Remaining individuals9 / 62,482 | 0.00014 |
| European (non-Finnish)31 / 1,179,924 | 2.6e-05 |
0 alternate alleles recorded in 7 other groups: Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, South Asian, African/African American.
gnomAD v2.1
AF 0.00016 · 40 / 250,942 alleles · 0 hom · FAF 2.9e-06
| Ashkenazi Jewish36 / 10,072 | 0.0036 |
| Remaining individuals2 / 6,116 | 0.00033 |
| European (non-Finnish)2 / 113,376 | 1.8e-05 |
0 alternate alleles recorded in 5 other groups: African/African American, Admixed American, East Asian, European (Finnish), South Asian.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 0.000100382; MAF= 0.01004%, 162/1613842 alleles, homozygotes = 0) and has highest observed frequency in the Ashkenazi Jewish population (AF= 0.00412246; MAF= 0.41225%, 122/29594 alleles, homozygotes = 0); grpmax FAF= 1.883e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000159399; MAF= 0.01594%, 40/250942 alleles, homozygotes = 0) and has highest observed frequency in the Ashkenazi Jewish population (AF= 0.00357427; MAF= 0.35743%, 36/10072 alleles, homozygotes = 0); grpmax FAF= 2.93e-06.
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 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 delta ≥ 0.20 for silent/missense/intronic variants. This variant is synonymous, located outside BRCA2 clinically important functional domains (aa 10-40 and aa 2481-3186), and SpliceAI max delta is 0.00. Neither pathway is satisfied. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.00 (no predicted splice impact).
- K1139 is outside BRCA2 clinically important functional domains (PALB2 binding: aa 10-40
- DNA binding: aa 2481-3186).
Sources
BP4 N/AENIGMA BP4 applies only to missense, in-frame, or silent variants inside a clinically important functional domain with no predicted impact. Residue K1139 is outside both BRCA2 clinically important functional domains (PALB2 binding aa 10-40 and DNA binding aa 2481-3186), so BP4 does not apply. Details ▾Hide ▴
Evidence considered
- K1139 is outside clinically important functional domains.
- ENIGMA BP4 rule requires variant to be inside a functional domain.
Sources
BP7 N/AENIGMA BP7_Supporting requires a silent variant inside a clinically important functional domain with BP4 met. BP7_Strong (RNA) requires well-established mRNA assay data showing no damaging effect. K1139 is outside the functional domains, BP4 is not met, and no variant-specific RNA assay data were identified. Details ▾Hide ▴
Evidence considered
- K1139 is outside clinically important functional domains
- BP4 prerequisite not met.
- No variant-specific mRNA assay data available for BP7_Strong(RNA).
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
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 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. · 2010The WECARE study screened 2,103 women with contralateral or unilateral breast cancer for BRCA1/2 variants and identified 470 unique sequence variants including 69 synonymous BRCA2 VUS. Aggregated synonymous BRCA2 VUS showed no statistically significant increase in contralateral breast cancer risk. The variant NM_000059.4:c.3417G>A was not individually reported.Does not name this variant
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PMID 23918944 ↗Tamoxifen and risk of contralateral breast cancer for BRCA1 and BRCA2 mutation carriers.This study investigated tamoxifen and contralateral breast cancer risk in BRCA1/2 mutation carriers using pooled observational cohort data. It analyzed only known deleterious BRCA1/2 mutations, not VUS or synonymous variants. NM_000059.4:c.3417G>A was not mentioned.Does not name this variant
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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.This is the ACMG/AMP 2015 standards and guidelines for sequence variant interpretation. It establishes the general framework for variant classification but does not discuss any specific BRCA2 variants.Does not name this variant
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PMID 17392385 ↗American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography.Saslow D et al. · 2007American Cancer Society guidelines for breast screening with MRI. Discusses screening recommendations for BRCA mutation carriers at the gene level but does not mention any specific BRCA2 variants.Does not name this variant
-
PMID 18163131 ↗The emerging landscape of breast cancer susceptibility.Stratton MR et al. · 2008Review of the genetic basis of inherited breast cancer susceptibility. Discusses BRCA2 at the gene level within the context of high-penetrance alleles but does not reference any specific BRCA2 variants.Does not name this variant
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PMID 20301425 ↗BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer.Adam MP et al. · 1993GeneReviews clinical summary for BRCA1/2-associated hereditary breast and ovarian cancer. No abstract available and no full text; expected to contain only gene-level clinical guidance without variant-specific data.Does not name this variant
-
PMID 23788249 ↗ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing.ACMG recommendations for reporting incidental findings in clinical exome and genome sequencing. Lists genes for which incidental findings should be reported (including BRCA2) but does not discuss specific variants.Does not name this variant
-
PMID 28492532 ↗Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.Sherloc refinement of ACMG-AMP variant classification criteria. Describes a classification framework but does not discuss specific BRCA2 variants. No abstract snippet available.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
162 / 1,613,842 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
8 Likely benign · 3 Benign · 1 Likely Benign
Open source ↗
COSMIC
Captured COSMIC source record
Open source ↗
Cancer hotspots
Captured Cancer Hotspots source record
Open source ↗
OncoKB
Captured OncoKB source record
Open source ↗
ClinGen CSpec
Captured ClinGen CSpec source record
Open source ↗
All source links
- ClinGen CSpec ↗cspec.genome.network/cspec/ui/svi/doc/1535438831
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/135796/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/13-32911909-G-A?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr13-32337772-G-A?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/13-32337772-G-A
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000059.4%3Ac.3417…
- OncoKB ↗www.oncokb.org/gene/BRCA2/K1139=
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=BRCA2+c.3417G%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= 0.000100382; MAF= 0.01004%, 162/1613842 alleles, homozygotes = 0) and has highest observed frequency in the Ashkenazi Jewish population (AF= 0.00412246; MAF= 0.41225%, 122/29594 alleles, homozygotes = 0); grpmax FAF= 1.883e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000159399; MAF= 0.01594%, 40/250942 alleles, homozygotes = 0) and has highest observed frequency in the Ashkenazi Jewish population (AF= 0.00357427; MAF= 0.35743%, 36/10072 alleles, homozygotes = 0); grpmax FAF= 2.93e-06.
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Likely benign (8 clinical laboratories) and as Benign (3 clinical laboratories) and as Likely Benign (1 clinical laboratory) and as Likely benign by Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) (expert panel). (ClinVarID = 135796)
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.