About BRCA2
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
BRCA2 c.425G>A, p.(Ser142Asn)
Classification
Uncertain significance
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is uncertain. Select a step to read what it means.
Uncertain.The recorded classification is uncertain significance.
In plain language
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.
LYFE Sciences is an AI system, and it can make mistakes.
Criteria may be applied incorrectly, sources may be misread, and a
confident-looking classification can still be wrong.
Double-check every criterion and its underlying evidence
before relying on any call.
01The reasoning
How it was classified
The recorded framework is ClinGen BRCA2 VCEP v1.2.0. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.
Recorded applied criteria
The applied criteria and their strengths are shown as assessed under the stated framework.
Pathogenic evidence criteria: 1
Benign evidence criteria: 1
Pathogenic criteria applied · 1
PP3Supporting
PP3 · supporting
SpliceAI predicts a splicing impact with a maximum delta score of 0.91, which exceeds the ENIGMA PP3 threshold of ≥0.2 for missense variants irrespective of location in clinically important functional domains. Per ENIGMA Figure 1A, PP3 Supporting is applied for missense variants with predicted splicing alteration (SpliceAI ≥0.2). The variant is annotated as missense_variant/splice_region_variant. The amino acid substitution (p.Ser142Asn) is located outside the BRCA2 clinically important functional domains (PALB2-binding aa 10-40; DNA-binding aa 2481-3186), so protein-level prediction (BayesDel no-AF = -0.314, REVEL = 0.153) is not used for PP3; the splicing prediction alone supports PP3.
Benign criteria applied · 1
BS1Supporting
BS1 · supporting
The gnomAD v4.1 grpmax filter allele frequency (FAF) is 0.00024125 (0.024%), which exceeds the ENIGMA BS1 Strong threshold of FAF >0.01% (FAF >0.0001). However, the ENIGMA v1.2 rule specifies gnomAD v2.1 and v3.1; the variant is absent from gnomAD v2.1 and confirmed present only in the newer v4.1 release. Given this version discrepancy, BS1 is applied at Supporting strength rather than Strong. The variant is observed in 44 of 1,544,990 alleles (AF=0.00285%), including 1 homozygote, with highest frequency in the South Asian population (30/89,438 alleles, AF=0.034%). These observations support that the variant is unlikely to be a highly penetrant pathogenic allele.
Recorded classification: Uncertain significance
ENIGMA BRCA1/BRCA2 v1.2.0 Table 3 conflicting-evidence point system: PP3_Supporting (+1 pathogenic point) + BS1_Supporting (-1 benign point) = 0 total points, which falls in the VUS range (-1 to 5). No other criteria are met. The single pathogenic supporting criterion and single benign supporting criterion are insufficient to reach Likely Pathogenic or Likely Benign thresholds under the ENIGMA all_of combination rules, and the point system resolves the conflict to VUS.
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
44 / 1,544,990 alleles
gnomAD v4.1: 44 / 1,544,990 alleles. Recorded AF 2.84791e-05. Recorded homozygote count 1.
gnomAD v2.1
Absent from gnomAD v2.1.
SpliceAI score
0.910 maximum delta
Recorded SpliceAI maximum delta score: 0.910. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
9 reported laboratory submissions
4 Uncertain significance · 3 Likely pathogenic · 2 Pathogenic.
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 v1.2.0, with the data and sources behind each one.
26 criteria with recorded statuses: 2 met · 8 not met · 6 not assessed · 10 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.425G>A (p.Ser142Asn) is a missense variant in BRCA2 exon 4, located outside the established clinically important functional domains (PALB2-binding domain aa 10-40; DNA-binding domain aa 2481-3186).
This variant is absent from gnomAD v2.1 but present in gnomAD v4.1 in 44 of 1,544,990 alleles (AF=0.00285%), including 1 homozygote, with a grpmax filter allele frequency of 0.024% (0.00024125). The highest subpopulation frequency is in the South Asian population (30/89,438 alleles, AF=0.034%).
SpliceAI predicts a splicing alteration with a maximum delta score of 0.91, exceeding the ENIGMA PP3 threshold of ≥0.2 for missense variants, supporting a potential splice effect (PP3_Supporting). However, the specific SpliceAI sub-scores (donor gain/loss, acceptor gain/loss) are not available, and no RNA splicing assay has been performed to confirm this prediction.
The population frequency evidence meets ENIGMA BS1 at Supporting strength: the grpmax FAF of 0.00024125 exceeds the 0.01% threshold, and the observation of a homozygous individual in gnomAD v4.1 argues against high-penetrance pathogenicity. The variant is absent from gnomAD v2.1 per the ENIGMA-specified dataset, but the larger v4.1 release confirms population presence.
Multifactorial likelihood analysis from Parsons et al. 2019 (PMID:31131967) yields a combined LR of 1.383 (neutral), with segregation LR=1.554 and pathology LR=0.89. Neither PP1 (co-segregation) nor BS4 (lack of segregation) thresholds are met. The clinical-history LR from Li et al. 2020 (PMID:31853058) is 1.027 (1 proband, neutral zone); PP4 and BP5 are not met.
The variant is not listed in ENIGMA Table 9 for calibrated functional assay results (PS3/BS3 not assessed). No variant-specific functional evidence was identified in the literature or in OncoKB.
In ClinVar, this variant is classified as Uncertain Significance by 4 clinical laboratories, as Likely Pathogenic by 3, and as Pathogenic by 2 (ClinVar Variation ID: 197099), with review status of criteria provided, single submitter and no expert panel classification.
Under the ENIGMA BRCA1/2 v1.2.0 combining rules (Table 3): PP3_Supporting (1 pathogenic supporting) and BS1_Supporting (1 benign supporting) are the only met criteria. Neither Likely Pathogenic nor Likely Benign thresholds are reached. The variant is classified as a Variant of Uncertain Significance (VUS).
No criteria match.
Met · 2
PP3 SupportingSpliceAI predicts a splicing impact with a maximum delta score of 0.91, which exceeds the ENIGMA PP3 threshold of ≥0.2 for missense variants irrespective of location in clinically important functional domains. Per ENIGMA Figure 1A, PP3 Supporting is applied for missense variants with predicted splicing alteration (SpliceAI ≥0.2). The variant is annotated as missense_variant/splice_region_variant. The amino acid substitution (p.Ser142Asn) is located outside the BRCA2 clinically important functional domains (PALB2-binding aa 10-40; DNA-binding aa 2481-3186), so protein-level prediction (BayesDel no-AF = -0.314, REVEL = 0.153) is not used for PP3; the splicing prediction alone supports PP3. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta=0.91 (≥0.2 threshold)
- variant in splice region
Still missing
- SpliceAI sub-scores (donor gain/loss
- acceptor gain/loss) are null
- max delta alone used. RNA splicing assay data would be needed to confirm predicted splice effect.
Sources
BS1 SupportingThe gnomAD v4.1 grpmax filter allele frequency (FAF) is 0.00024125 (0.024%), which exceeds the ENIGMA BS1 Strong threshold of FAF >0.01% (FAF >0.0001). However, the ENIGMA v1.2 rule specifies gnomAD v2.1 and v3.1; the variant is absent from gnomAD v2.1 and confirmed present only in the newer v4.1 release. Given this version discrepancy, BS1 is applied at Supporting strength rather than Strong. The variant is observed in 44 of 1,544,990 alleles (AF=0.00285%), including 1 homozygote, with highest frequency in the South Asian population (30/89,438 alleles, AF=0.034%). These observations support that the variant is unlikely to be a highly penetrant pathogenic allele. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1: 44 alleles
- 1 homozygote
- grpmax FAF=0.00024125 (>0.0001 ENIGMA threshold)
- South Asian AF=0.034%
Still missing
- ENIGMA BS1 rule references gnomAD v2.1/v3.1
- v2.1 shows absent. v4.1 FAF used as best available population frequency evidence.
Sources
Not met · 8 · evaluated, threshold not reached
PM2 The variant is absent from gnomAD v2.1 (exome), but is present in gnomAD v4.1 with 44 alleles (AF=2.85e-05), including 1 homozygote, and a grpmax FAF of 0.00024125. The presence in the larger v4.1 dataset (1,544,990 alleles) indicates the variant is not truly absent from outbred population controls. ENIGMA PM2 (Supporting) requires absence from both gnomAD v2.1 and v3.1; the v4.1 data supersedes and shows presence. PM2 is therefore not met. Details ▾Hide ▴
Evidence considered
- Absent from gnomAD v2.1
- present in gnomAD v4.1 (44 alleles
- 1 homozygote
- grpmax FAF=0.00024125)
Still missing
- gnomAD v3.1 data not directly assessed
- v4.1 supersedes
Sources
PP1 The co-segregation likelihood ratio from the Parsons et al. 2019 (PMID:31131967) multifactorial analysis is 1.5539, which falls below the ENIGMA PP1 Supporting threshold of LR ≥2.08. This does not provide sufficient evidence for co-segregation with disease. Details ▾Hide ▴
Evidence considered
- Segregation LR=1.5539 from Parsons et al. 2019 SuppT1
- below PP1 Supporting threshold (LR≥2.08)
Still missing
- Only 1 co-segregation family in kConFab dataset
Sources
PP4 The clinical-history likelihood ratio from Li et al. 2020 (PMID:31853058) is 1.027 (1 proband), which falls in the ENIGMA neutral zone (>0.48 and <2.08). The combined multifactorial LR from Parsons et al. 2019 is 1.383, also neutral. Neither meets the PP4 Supporting threshold of LR ≥2.08. PP4 is not met. Details ▾Hide ▴
Evidence considered
- Clinical history LR=1.027 (1 proband
- PMID:31853058)
- combined multifactorial LR=1.383 (PMID:31131967)
- both in neutral zone
Still missing
- Only 1 proband with clinical history data
- additional probands needed
Sources
vcep_pmid_31853058_brca2_clinical_history_lrPMID:31853058 ↗vcep_humu_40_1557_s001PMID:31131967 ↗3113196731853058
BA1 The gnomAD v4.1 grpmax filter allele frequency (FAF) is 0.00024125 (0.024%), which is below the ENIGMA BA1 threshold of >0.1% (FAF >0.001). BA1 Stand-Alone is not met. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 grpmax FAF=0.00024125
- below BA1 threshold of >0.001
Sources
BS4 The segregation likelihood ratio from Parsons et al. 2019 is 1.5539, which is above the ENIGMA BS4 Supporting threshold of LR ≤0.48. This does not support lack of segregation with disease. BS4 is not met. Details ▾Hide ▴
Evidence considered
- Segregation LR=1.5539
- above BS4 Supporting threshold (LR≤0.48)
Sources
BP1 BP1_Strong requires a missense variant outside clinically important functional domains AND no splicing predicted (SpliceAI ≤0.1). While this variant is located outside the BRCA2 functional domains (PALB2-binding aa 10-40; DNA-binding aa 2481-3186), SpliceAI predicts a splicing alteration with max delta score of 0.91, which exceeds the 0.1 threshold. BP1 is not met due to predicted splicing impact. Details ▾Hide ▴
Evidence considered
- Variant outside functional domains (aa142)
- SpliceAI=0.91 exceeds BP1 threshold of ≤0.1
Sources
BP4 ENIGMA BP4 for missense variants applies only when inside a clinically important functional domain with no predicted impact via protein change (BayesDel no-AF ≤0.18) AND no predicted splicing (SpliceAI ≤0.1). This variant is outside the functional domains, and SpliceAI predicts a splicing alteration (max delta=0.91), which exceeds the BP4 threshold of ≤0.1. BP4 is not met. Details ▾Hide ▴
Evidence considered
- Outside functional domains
- SpliceAI=0.91 (>0.1 threshold)
- BayesDel=-0.314 (≤0.18 would be met for protein
- but splice prediction is positive)
Sources
BP5 The clinical-history likelihood ratio from Li et al. 2020 is 1.027 (1 proband), which is above the ENIGMA BP5 Supporting threshold of LR ≤0.48. The combined multifactorial LR from Parsons et al. 2019 is 1.383, also above the threshold. Neither supports benignity via clinical history. BP5 is not met. Details ▾Hide ▴
Evidence considered
- Clinical history LR=1.027 (above BP5 Supporting threshold of ≤0.48)
- combined multifactorial LR=1.383 (also above threshold)
Sources
vcep_pmid_31853058_brca2_clinical_history_lrPMID:31853058 ↗vcep_humu_40_1557_s001PMID:31131967 ↗3113196731853058
Not assessed · 6 · no assessment recorded
PS1 No previously classified pathogenic variant with the same amino acid change (Ser142Asn) was identified. No comparator variant at this residue with a definitive pathogenic classification is available in the VCEP materials or ClinVar. Details ▾Hide ▴
Evidence considered
- No pathogenic comparator at same residue identified
Still missing
- May exist in curated databases not yet reviewed
PS3 The variant is not listed in ENIGMA Specifications Table 9 (curated functional assay results). No calibrated functional assay data from well-established in vitro or in vivo studies measuring protein function were identified. The OncoKB entry notes gene-level curated context but no variant-specific functional evidence. Details ▾Hide ▴
Evidence considered
- Absent from ENIGMA Table 9 functional assay results
- no variant-specific functional evidence identified
Still missing
- No calibrated functional assay data available for this variant
Sources
vcep_specifications_table9_v1_2_2024_11_18oncokb ↗
PS4 No case-control study with an odds ratio meeting ENIGMA criteria (OR ≥4, lower CI excluding 2.0, p ≤0.05) was identified for this variant. The variant has been observed in gnomAD with 44 alleles and in clinical testing cohorts, but no formal case-control comparison is available. Details ▾Hide ▴
Evidence considered
- No case-control OR data available
Still missing
- No published case-control study for this variant
Sources
gnomad_v4 ↗vcep_humu_40_1557_s001
BS2 BS2 requires proband-level assessment of Fanconi Anemia (FA) phenotype absence with a point-based system per ENIGMA Specifications Table 8. The gnomAD v4.1 observation of a homozygous individual suggests possible healthy adult carrier, but individual-level clinical data confirming the absence of FA features are not available. Insufficient data to apply BS2. Details ▾Hide ▴
Evidence considered
- 1 homozygous individual observed in gnomAD v4.1
- no FA phenotyping data available
Still missing
- No proband-level clinical data to exclude Fanconi Anemia phenotype
Sources
BS3 The variant is not listed in ENIGMA Specifications Table 9 (curated functional assay results for PS3/BS3). No well-established in vitro or in vivo functional studies demonstrating no damaging effect on protein function were identified. BS3 cannot be assessed without calibrated functional assay data. Details ▾Hide ▴
Evidence considered
- Absent from ENIGMA Table 9
- no functional assay data available
Still missing
- No calibrated functional assay data for this variant
Sources
vcep_specifications_table9_v1_2_2024_11_18
PS5 No alternative missense variant at the same amino acid residue (Ser142) with a definitive pathogenic classification was identified in VCEP materials or ClinVar. No ENIGMA-specific PS5 rule exists; assessed under generic ACMG/AMP framework. Insufficient evidence to apply PS5. Details ▾Hide ▴
Evidence considered
- No pathogenic comparator at same residue with different amino acid change identified
Still missing
- No curated comparator variant at Ser142
Not applicable · 10· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/APVS1 is not applicable: this is a missense substitution (p.Ser142Asn), not a null variant (nonsense, frameshift, or canonical ±1,2 splice site). ENIGMA PVS1 rules apply only to null variants and variants with demonstrated RNA-level splicing impact. Details ▾Hide ▴
Evidence considered
- Missense variant not eligible for PVS1 under ENIGMA v1.2 null-variant rules
Sources
vcep_specifications_v1_2_2024_11_18
PS2 VCEPPS2 is designated Not Applicable under the ENIGMA BRCA1/2 specification v1.2.0. Details ▾Hide ▴
PM1 VCEPPM1 is designated Not Applicable under the ENIGMA BRCA1/2 specification v1.2.0. Details ▾Hide ▴
PM5 N/AUnder ENIGMA v1.2, PM5 is repurposed exclusively for PTC (protein termination codon) variants in exons where a different proven pathogenic PTC variant has been observed (PM5_PTC). This is a missense variant and does not qualify for ENIGMA PM5_PTC adjudication. Details ▾Hide ▴
Evidence considered
- Missense variant
- ENIGMA PM5 applies only to PTC variants
Sources
vcep_specifications_table4_v1_2_2024_11_18cspec ↗
PM6 VCEPPM6 is designated Not Applicable under the ENIGMA BRCA1/2 specification v1.2.0. Details ▾Hide ▴
PP2 VCEPPP2 is designated Not Applicable under the ENIGMA BRCA1/2 specification v1.2.0. Details ▾Hide ▴
PP5 VCEPPP5 is designated Not Applicable under the ENIGMA BRCA1/2 specification v1.2.0. Details ▾Hide ▴
BP2 VCEPBP2 is designated Not Applicable under the ENIGMA BRCA1/2 specification v1.2.0. Details ▾Hide ▴
BP6 VCEPBP6 is designated Not Applicable under the ENIGMA BRCA1/2 specification v1.2.0. Details ▾Hide ▴
BP7 N/AENIGMA BP7_Supporting applies only to silent or intronic variants meeting specific criteria. This is a missense variant. BP7_Strong (RNA) requires well-established mRNA assay evidence showing no damaging effect on splicing, which is not available for this variant. BP7 is not applicable. Details ▾Hide ▴
Evidence considered
- Missense variant
- no mRNA assay data for BP7_Strong(RNA)
- BP7_Supporting restricted to silent/intronic
Still missing
- RNA splicing assay would clarify if predicted splice effect is functional
Sources
Identifiers
- Gene
- BRCA2
- Transcript
- NM_000059.4
- Coding (HGVS c.)
- NM_000059.4:c.425G>A
- Protein (HGVS p.)
- NP_000050.3:p.(Ser142Asn)
- GRCh38
- chr13:32325184 G>A
- GRCh37
- chr13:32899321 G>A
- ClinVar
- 197099, 142617
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
44 / 1,544,990 alleles
AF 2.85e-05 · 1 homozygotes · FAF 0.000241
gnomAD v2.1
Allele count data not recorded
gnomAD-Canada v1.0
0 / 0 alleles
AF 0 · 0 homozygotes · FAF 0
By genetic ancestry
gnomAD v4.1
AF 2.8e-05 · 44 / 1,544,990 alleles · 1 hom · FAF 0.00024
| South Asian30 / 89,438 | 0.000341 hom |
| European (non-Finnish)14 / 1,118,544 | 1.3e-05 |
0 alternate alleles recorded in 8 other groups: Remaining individuals, Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, Ashkenazi Jewish, African/African American.
gnomAD-Canada
AF 0 · 0 / 0 alleles · 0 hom
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 2.84791e-05; MAF= 0.00285%, 44/1544990 alleles, homozygotes = 1) and has highest observed frequency in the South Asian population (AF= 0.000335428; MAF= 0.03354%, 30/89438 alleles, homozygotes = 1); grpmax FAF= 0.00024125.
gnomAD v2.1
Absent from gnomAD v2.1.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.153
- BayesDel
- -0.314
How the predictions were used
PP3 SupportingSpliceAI predicts a splicing impact with a maximum delta score of 0.91, which exceeds the ENIGMA PP3 threshold of ≥0.2 for missense variants irrespective of location in clinically important functional domains. Per ENIGMA Figure 1A, PP3 Supporting is applied for missense variants with predicted splicing alteration (SpliceAI ≥0.2). The variant is annotated as missense_variant/splice_region_variant. The amino acid substitution (p.Ser142Asn) is located outside the BRCA2 clinically important functional domains (PALB2-binding aa 10-40; DNA-binding aa 2481-3186), so protein-level prediction (BayesDel no-AF = -0.314, REVEL = 0.153) is not used for PP3; the splicing prediction alone supports PP3. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta=0.91 (≥0.2 threshold)
- variant in splice region
Still missing
- SpliceAI sub-scores (donor gain/loss
- acceptor gain/loss) are null
- max delta alone used. RNA splicing assay data would be needed to confirm predicted splice effect.
Sources
BP4 ENIGMA BP4 for missense variants applies only when inside a clinically important functional domain with no predicted impact via protein change (BayesDel no-AF ≤0.18) AND no predicted splicing (SpliceAI ≤0.1). This variant is outside the functional domains, and SpliceAI predicts a splicing alteration (max delta=0.91), which exceeds the BP4 threshold of ≤0.1. BP4 is not met. Details ▾Hide ▴
Evidence considered
- Outside functional domains
- SpliceAI=0.91 (>0.1 threshold)
- BayesDel=-0.314 (≤0.18 would be met for protein
- but splice prediction is positive)
Sources
BP7 N/AENIGMA BP7_Supporting applies only to silent or intronic variants meeting specific criteria. This is a missense variant. BP7_Strong (RNA) requires well-established mRNA assay evidence showing no damaging effect on splicing, which is not available for this variant. BP7 is not applicable. Details ▾Hide ▴
Evidence considered
- Missense variant
- no mRNA assay data for BP7_Strong(RNA)
- BP7_Supporting restricted to silent/intronic
Still missing
- RNA splicing assay would clarify if predicted splice effect is functional
Sources
Statement
In silico
SpliceAI predicts possible splice impact for this variant (max delta score = 0.91). REVEL score = 0.153. BayesDel score = -0.314007.
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 21638052 ↗Characterisation of unclassified variants in the BRCA1/2 genes with a putative effect on splicing.Brandão RD et al. · 2011No paper-specific finding is recorded.
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PMID 17576681 ↗Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.Buratti E et al. · 2007No paper-specific finding is recorded.
-
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.
-
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 31131967 ↗Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification.Parsons MT et al. · 2019No paper-specific finding is recorded.
-
PMID 32398771 ↗Alternative mRNA splicing can attenuate the pathogenicity of presumed loss-of-function variants in BRCA2.Mesman RLS et al. · 2020No paper-specific finding is recorded.
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PMID 32853339 ↗Germline Sequencing DNA Repair Genes in 5545 Men With Aggressive and Nonaggressive Prostate Cancer.Darst BF et al. · 2021No paper-specific finding is recorded.
-
PMID 28492532 ↗Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.No paper-specific finding is recorded.
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
44 / 1,544,990 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.910
Open source ↗
ClinVar
4 Uncertain significance · 3 Likely pathogenic · 2 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/197099/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/13-32899321-G-A?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr13-32325184-G-A?dataset=gn…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000059.4%3Ac.425G…
- OncoKB ↗www.oncokb.org/gene/BRCA2/S142N
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=BRCA2+c.425G%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= 2.84791e-05; MAF= 0.00285%, 44/1544990 alleles, homozygotes = 1) and has highest observed frequency in the South Asian population (AF= 0.000335428; MAF= 0.03354%, 30/89438 alleles, homozygotes = 1); grpmax FAF= 0.00024125.
gnomAD v2.1
Absent from gnomAD v2.1.
ClinVar
This variant has been reported in ClinVar as Uncertain significance (4 clinical laboratories) and as Likely pathogenic (3 clinical laboratories) and as Pathogenic (2 clinical laboratories). (ClinVarID = 197099)
In silico
SpliceAI predicts possible splice impact for this variant (max delta score = 0.91). REVEL score = 0.153. BayesDel score = -0.314007.
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.