About BRCA1
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
BRCA1 c.5090G>A, p.(Cys1697Tyr)
Classification
Likely pathogenic
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is likely pathogenic. Select a step to read what it means.
Likely pathogenic.A likely pathogenic classification under the recorded framework.
In plain language
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.
LYFE Sciences is an AI system, and it can make mistakes.
Criteria may be applied incorrectly, sources may be misread, and a
confident-looking classification can still be wrong.
Double-check every criterion and its underlying evidence
before relying on any call.
01The reasoning
How it was classified
The recorded framework is ClinGen BRCA1 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: 3
Benign evidence criteria: 0
Pathogenic criteria applied · 3
PS3Strong
PS3 · strong
This BRCA1 missense variant has calibrated functional evidence showing damaging protein effect. ENIGMA Table 9 lists c.5090G>A p.(Cys1697Tyr) as PS3 Strong, with two calibrated studies reporting protein function similar to pathogenic controls; the supplementary functional dataset also records a complete functional impact/loss-of-function result. This supports PS3 at Strong strength.
PM2Supporting
PM2 · supporting
This variant is absent from the retrieved gnomAD v2.1 and gnomAD v4.1 datasets, corresponding to observed allele frequency 0 in both datasets. This is below the ENIGMA absence/rarity requirement for PM2_Supporting and supports PM2 at Supporting strength, assuming adequate local coverage.
PP3Supporting
PP3 · supporting
This variant is a missense substitution within the BRCA1 BRCT repeat domain, a clinically important functional domain spanning amino acids 1650-1857. The bioinformatic dataset reports BayesDel no-AF approximately 0.386-0.39, which is above the ENIGMA PP3 threshold of ≥0.28, and SpliceAI max delta score is 0.03, below the splice-impact threshold of ≥0.2. These findings support a deleterious protein effect without predicted splicing impact, meeting PP3 at Supporting strength.
Benign criteria applied · 0
No benign criterion marked as applied in the recorded assessment.
Recorded classification: Likely pathogenic
ENIGMA BRCA1 and BRCA2 Specification v1.2.0 Table 3 adapted ACMG/AMP criteria-combination framework was used. Applied pathogenic evidence comprises 1 Strong criterion (PS3) and 2 Supporting criteria (PM2, PP3), with no benign criteria met.
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
Not recorded
gnomAD v4.1 allele counts were not recorded for this variant.
gnomAD v2.1
Absent from gnomAD v2.1.
No screenshot for this evidence
Computational predictions
Not recorded
No SpliceAI or REVEL score is recorded in the fields used for this tile.
ClinVar submissions
Not recorded
A ClinVar laboratory submission summary was not recorded.
Context only
ClinVar ↗
Functional evidence
Statement recorded
OncoKB has not reviewed this specific variant; no variant-level oncogenicity or biological effect is available. Gene-level context: BRCA1, a tumor suppressor involved in the DNA damage response, is mutated in various cancer types.
COSMIC
Cancer Hotspots
Somatic evidence
Not assessed
No COSMIC evidence statement is recorded in this case.
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under ClinGen BRCA1 VCEP v1.2.0, with the data and sources behind each one.
28 criteria with recorded statuses: 3 met · 5 not met · 8 not assessed · 12 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
The BRCA1 c.5090G>A (p.Cys1697Tyr; C1697Y) variant has been reported in ClinVar as likely pathogenic by the ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel, with additional clinical-laboratory submissions including likely pathogenic, pathogenic, and uncertain significance.
This variant is absent from the retrieved gnomAD v2.1 and gnomAD v4.1 population datasets, supporting PM2 at Supporting strength and arguing against BA1 or BS1 frequency-based benign evidence.
Calibrated ENIGMA functional evidence reports BRCA1 c.5090G>A p.(Cys1697Tyr) as PS3 Strong, with supplementary functional data recording complete functional impact and loss-of-function behavior.
The variant affects residue 1697 within the BRCA1 BRCT repeats, a clinically important domain, has BayesDel no-AF approximately 0.386-0.39 above the ENIGMA PP3 threshold of ≥0.28, and has SpliceAI max delta 0.03 below the predicted splice-impact threshold.
No criteria match.
Met · 3
PS3 StrongThis BRCA1 missense variant has calibrated functional evidence showing damaging protein effect. ENIGMA Table 9 lists c.5090G>A p.(Cys1697Tyr) as PS3 Strong, with two calibrated studies reporting protein function similar to pathogenic controls; the supplementary functional dataset also records a complete functional impact/loss-of-function result. This supports PS3 at Strong strength. Details ▾Hide ▴
Rule
Well-established in vitro or in vivo functional studies supportive of a damaging effect; apply PS3 for protein-only or combined mRNA/protein assays, with recommendations from ENIGMA Table 9.
Evidence considered
- ENIGMA Table 9: BRCA1 c.5090G>A p.(Cys1697Tyr)
- PS3 Strong
- two calibrated studies
- Supplementary Table ST4: c.5090G>A
- Functional impact - complete
- LOF
- IARC class 5/pathogenic.
Sources
vcep_s_p_e_c_i_f_i_c_a_t_i_o_n_s___t_a_b_l_e_9___v_1___2___2_0_2_4___1_1___1_8vcep_s_u_p_p_l_e_m_e_n_t_a_r_y_t_a_b_l_e_s___v_1___2___2_0_2_4___1_1___1_8cspec ↗
PM2 SupportingThis variant is absent from the retrieved gnomAD v2.1 and gnomAD v4.1 datasets, corresponding to observed allele frequency 0 in both datasets. This is below the ENIGMA absence/rarity requirement for PM2_Supporting and supports PM2 at Supporting strength, assuming adequate local coverage. Details ▾Hide ▴
Rule
Absent from controls in an outbred population from gnomAD v2.1 non-cancer exome subset and gnomAD v3.1 non-cancer, with regional average read depth ≥25; ENIGMA strength PM2_Supporting.
Evidence considered
- gnomAD v2.1: absent
- gnomAD v4.1: absent.
Still missing
- Average read depth around the variant was not explicitly shown in the retrieved gnomAD summary.
Sources
PP3 SupportingThis variant is a missense substitution within the BRCA1 BRCT repeat domain, a clinically important functional domain spanning amino acids 1650-1857. The bioinformatic dataset reports BayesDel no-AF approximately 0.386-0.39, which is above the ENIGMA PP3 threshold of ≥0.28, and SpliceAI max delta score is 0.03, below the splice-impact threshold of ≥0.2. These findings support a deleterious protein effect without predicted splicing impact, meeting PP3 at Supporting strength. Details ▾Hide ▴
Rule
Apply PP3 for missense variants inside a clinically important functional domain with predicted protein impact, BayesDel no-AF ≥0.28; apply PP3 for predicted splicing when SpliceAI ≥0.2.
Evidence considered
- Supplementary bioinformatic tables: c.5090G>A p.Cys1697Tyr in BRCT repeats
- BayesDel no-AF 0.386406/0.39
- SpliceAI max delta 0.03.
Sources
vcep_s_u_p_p_l_e_m_e_n_t_a_r_y_t_a_b_l_e_s___v_1___2___2_0_2_4___1_1___1_8spliceai ↗cspec ↗vcep_a_p_p_e_n_d_i_c_e_s___v_1___2___2_0_2_4___1_1___1_8
Not met · 5 · evaluated, threshold not reached
BA1 This variant is absent from the retrieved gnomAD v2.1 and v4.1 datasets, with observed frequency 0. This is below, not above, the ENIGMA BA1 threshold of FAF >0.1% (>0.001), so BA1 is not met. Details ▾Hide ▴
Rule
BA1 applies when filter allele frequency is >0.1% (FAF >0.001) in a non-founder gnomAD population.
Evidence considered
- gnomAD v2.1 absent
- gnomAD v4.1 absent.
Sources
BS1 This variant is absent from the retrieved gnomAD v2.1 and v4.1 datasets, with observed frequency 0. This is below the ENIGMA BS1 thresholds of FAF >0.002% for Supporting or >0.01% for Strong, so BS1 is not met. Details ▾Hide ▴
Rule
BS1_Supporting applies for FAF >0.002% and ≤0.01%; BS1_Strong applies for FAF >0.01% in a non-founder gnomAD population.
Evidence considered
- gnomAD v2.1 absent
- gnomAD v4.1 absent.
Sources
BS3 Available calibrated functional evidence supports damaging protein effect rather than normal function. Therefore benign functional evidence criterion BS3 is not met. Details ▾Hide ▴
Rule
BS3 applies when well-established functional studies show no damaging effect on protein function; RNA-only benign splicing evidence is handled through BP7.
Evidence considered
- ENIGMA Table 9 assigns PS3 Strong
- Supplementary Table ST4 records complete functional impact/loss-of-function.
Sources
vcep_s_p_e_c_i_f_i_c_a_t_i_o_n_s___t_a_b_l_e_9___v_1___2___2_0_2_4___1_1___1_8vcep_s_u_p_p_l_e_m_e_n_t_a_r_y_t_a_b_l_e_s___v_1___2___2_0_2_4___1_1___1_8cspec ↗
BP1 This variant is a missense substitution within the BRCA1 BRCT repeat region, which is a clinically important functional domain. BP1_Strong requires a missense, synonymous, or in-frame variant outside a clinically important functional domain with SpliceAI ≤0.1; because p.Cys1697Tyr is inside the BRCT domain, BP1 is not met. Details ▾Hide ▴
Rule
Apply BP1_Strong for silent, missense, or in-frame variants outside a clinically important functional domain and no splicing predicted, SpliceAI ≤0.1.
Evidence considered
- BRCA1 BRCT repeats are defined as aa 1650-1857
- variant affects residue 1697
- SpliceAI max delta 0.03.
Sources
BP4 This variant is inside a clinically important BRCA1 functional domain and has BayesDel no-AF approximately 0.386-0.39, which is above the benign BP4 threshold of ≤0.15. Although SpliceAI max delta score is 0.03 and therefore below the no-splice-impact threshold of ≤0.1, the protein-impact prediction does not support BP4. BP4 is not met. Details ▾Hide ▴
Rule
For missense variants inside a clinically important functional domain, BP4 requires BayesDel no-AF ≤0.15 and SpliceAI ≤0.1.
Evidence considered
- BayesDel no-AF 0.386406/0.39
- SpliceAI max delta 0.03.
Sources
Not assessed · 8 · no assessment recorded
PS1 No independent evidence was identified that a different nucleotide change produces the same p.(Cys1697Tyr) amino acid change and has been classified as pathogenic by the ENIGMA specification. PS1 was therefore not applied. Details ▾Hide ▴
Rule
Apply PS1 for a missense substitution with the same amino-acid change as a previously classified pathogenic variant, with no confirmed or predicted splicing effect; PS1_Moderate for a likely pathogenic comparator.
Evidence considered
- ClinVar identifies the same c.5090G>A variant
- but this does not by itself satisfy PS1 for a different nucleotide change with the same amino acid effect.
Still missing
- A targeted search for alternative nucleotide substitutions producing p.Cys1697Tyr was not documented.
Sources
PS4 No case-control dataset with p-value ≤0.05, odds ratio ≥4, and lower confidence interval excluding 2.0 was identified for this variant. PS4 was not applied. Details ▾Hide ▴
Rule
Case-control studies with p-value ≤0.05 and OR ≥4, with lower confidence interval excluding 2.0.
Evidence considered
- ClinVar reports the variant but does not provide a qualifying ENIGMA PS4 case-control calculation in the reviewed evidence.
Still missing
- No qualifying case-control odds ratio or likelihood-ratio dataset was available for direct adjudication.
Sources
PM3 No evidence was identified that this variant occurs in trans with a pathogenic BRCA1 variant in an individual with a BRCA1/2-related Fanconi anemia phenotype. PM3 was not applied. Details ▾Hide ▴
Rule
Apply for patients with phenotype consistent with BRCA1/2-related Fanconi anemia and co-occurring variants in the same gene, scored by ENIGMA Table 6.
Evidence considered
- No qualifying PM3 case observations were present in the reviewed evidence.
Still missing
- No proband-level co-occurrence
- phase
- or Fanconi anemia phenotype data were available.
Sources
PP1 No quantitative co-segregation analysis or family segregation likelihood ratio was identified for this variant. PP1 was not applied. Details ▾Hide ▴
Rule
Co-segregation with disease measured by quantitative co-segregation analysis; PP1 strength is assigned by likelihood ratio thresholds.
Evidence considered
- No qualifying segregation data were present in the reviewed evidence.
Still missing
- No segregation likelihood ratio or informative family data were available.
Sources
PP4 No multifactorial likelihood ratio based on clinical features, family history, tumor pathology, co-occurrence, or related calibrated clinical data was identified. PP4 was not applied. Details ▾Hide ▴
Rule
Use only to capture calibrated multifactorial likelihood evidence toward pathogenicity; PP4 thresholds are LR ≥2.08, ≥4.3, ≥18.7, or ≥350 depending on strength.
Evidence considered
- No PP4 likelihood-ratio evidence was present in the reviewed evidence.
Still missing
- No calibrated multifactorial likelihood ratio was available.
Sources
BS2 No evidence was identified that this variant was observed in unaffected adults or in contexts supporting the ENIGMA BS2 point framework. BS2 was not applied. Details ▾Hide ▴
Rule
Applied in absence of features of recessive disease using ENIGMA Table 8 point thresholds; BS2 requires ≥4 points, BS2_Moderate 2 points, BS2_Supporting 1 point.
Evidence considered
- No qualifying BS2 evidence was present in the reviewed evidence.
Still missing
- No qualifying unaffected-carrier or co-occurrence data were available.
Sources
BS4 No quantitative evidence of lack of segregation in affected family members was identified. BS4 was not applied. Details ▾Hide ▴
Rule
Lack of segregation with disease measured by quantitative co-segregation analysis; BS4 strength is assigned by likelihood ratio thresholds.
Evidence considered
- No qualifying BS4 evidence was present in the reviewed evidence.
Still missing
- No co-segregation likelihood ratio showing lack of segregation was available.
Sources
BP5 No calibrated multifactorial likelihood ratio against pathogenicity was identified for this variant. BP5 was not applied. Details ▾Hide ▴
Rule
Use only to capture calibrated multifactorial likelihood evidence against pathogenicity; BP5 strength is assigned by LR thresholds.
Evidence considered
- No qualifying BP5 evidence was present in the reviewed evidence.
Still missing
- No multifactorial likelihood ratio ≤0.48
- ≤0.23
- ≤0.05
- or ≤0.00285 was available.
Sources
Not applicable · 12· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/AThis variant is a missense substitution, NP_009225.1:p.(Cys1697Tyr), rather than a nonsense, frameshift, canonical ±1/2 splice, initiation-codon, or exon-level deletion variant. Although BRCA1 loss of function is an established disease mechanism, PVS1 is not applicable to this missense change under the ENIGMA BRCA1/2 specification. Details ▾Hide ▴
Rule
Null variant in BRCA1 where loss of function is a known mechanism, with strength assigned by ENIGMA PVS1 flowchart/Table 4; not applicable to ordinary missense variants without qualifying RNA-loss evidence.
Evidence considered
- BRCA1 VCEP/CSPEC PVS1 rule applies to null variants or damaging mRNA-only functional evidence
- pvs1_variant_assessment identifies this variant as outside null-variant PVS1 buckets.
Sources
PS2 N/AThe ENIGMA BRCA1/2 specification does not use de novo evidence for BRCA1/2-related cancers because these cancers are relatively common and de novo predictive value is not calibrated. PS2 is not applicable. Details ▾Hide ▴
Rule
PS2 is not applicable for this VCEP.
Evidence considered
- CSPEC marks PS2 as not applicable for this VCEP.
Sources
PM1 N/AAlthough p.Cys1697Tyr lies within the clinically important BRCA1 BRCT repeat region, the ENIGMA BRCA1/2 specification treats domain/location information as part of the PP3/BP4 bioinformatic framework rather than applying PM1 as a separate criterion. PM1 is not applicable. Details ▾Hide ▴
Rule
PM1 is not applicable for this VCEP; domain information is considered within PP3/BP4.
Evidence considered
- CSPEC marks PM1 not applicable
- ENIGMA appendices define BRCA1 BRCT repeats aa 1650-1857 as clinically important domains used in bioinformatic code application.
Sources
cspec ↗vcep_a_p_p_e_n_d_i_c_e_s___v_1___2___2_0_2_4___1_1___1_8
PM4 N/AThis variant is a single amino-acid substitution and does not alter protein length. The ENIGMA BRCA1/2 specification also treats PM4 as not applicable, with protein-change context handled through the bioinformatic framework. PM4 is not applicable. Details ▾Hide ▴
Rule
PM4 is not applicable for this VCEP.
Evidence considered
- CSPEC marks PM4 not applicable.
Sources
PM5 N/AThe ENIGMA BRCA1/2 PM5 criterion is specified for protein termination codon variants used with PVS1, not for this missense substitution. PM5_PTC is therefore not applicable. Details ▾Hide ▴
Rule
Protein termination codon variant in an exon where a different proven pathogenic PTC variant has been seen before; not applicable to missense variants.
Evidence considered
- The variant is p.Cys1697Tyr
- not a protein termination codon
- Table 4 PM5_PTC applies to PTC variants by exon.
Sources
cspec ↗vcep_s_p_e_c_i_f_i_c_a_t_i_o_n_s___t_a_b_l_e_4___v_1___2___2_0_2_4___1_1___1_8
PM6 N/AThe ENIGMA BRCA1/2 specification does not use assumed de novo evidence for BRCA1/2-related cancers. PM6 is not applicable. Details ▾Hide ▴
Rule
PM6 is not applicable for this VCEP.
Evidence considered
- CSPEC marks PM6 as not applicable.
Sources
PP2 N/AThe ENIGMA BRCA1/2 specification marks PP2 as not applicable because BRCA1 has a high frequency of benign missense variation. PP2 is not applicable. Details ▾Hide ▴
Rule
PP2 is not applicable for this VCEP.
Evidence considered
- CSPEC marks PP2 not applicable.
Sources
PP5 N/AAlthough ClinVar includes an ENIGMA expert-panel likely pathogenic assertion for this variant, the ENIGMA BRCA1/2 specification states that PP5 is not used. PP5 is not applicable. Details ▾Hide ▴
BP2 N/AThe ENIGMA BRCA1/2 specification applies BP2 only in the context of BS2, and no BS2 evidence was identified. BP2 is not applicable. Details ▾Hide ▴
Rule
BP2 is applied only in the context of BS2 for this VCEP.
Evidence considered
- CSPEC marks BP2 not applicable except in the context of BS2.
Sources
BP3 N/AThis variant is not an in-frame deletion or insertion in a repetitive region, and the ENIGMA BRCA1/2 specification marks BP3 as not applicable. BP3 is not applicable. Details ▾Hide ▴
Rule
BP3 is not applicable for this VCEP.
Evidence considered
- CSPEC marks BP3 not applicable.
Sources
BP6 N/AThe ENIGMA BRCA1/2 specification states that BP6 is not used. BP6 is not applicable. Details ▾Hide ▴
Rule
BP6 is not used by this VCEP as recommended by ClinGen SVI.
Evidence considered
- CSPEC marks BP6 as not applicable for this VCEP.
Sources
BP7 N/AThis variant is a missense substitution within a clinically important BRCA1 functional domain. BP7 is intended for qualifying benign mRNA-only evidence in intronic, synonymous, or missense/in-frame variants outside clinically important domains, or for domain missense variants only when BS3 is also met; BS3 is not met. BP7 is therefore not applicable. Details ▾Hide ▴
Rule
BP7 applies to well-established mRNA-only evidence showing no damaging effect in specified variant contexts; domain missense variants require BS3 eligibility.
Evidence considered
- SpliceAI max delta 0.03 indicates no predicted splice impact
- but no qualifying benign mRNA-only assay evidence or BS3 evidence was identified.
Sources
Identifiers
- Gene
- BRCA1
- Transcript
- NM_007294.4
- Coding (HGVS c.)
- NM_007294.4:c.5090G>A
- Protein (HGVS p.)
- NP_009225.1:p.(Cys1697Tyr)
- GRCh38
- chr17:43063936 C>T
- GRCh37
- chr17:41215953 C>T
Gene diagram
Every interpreted variant in BRCA1, mapped onto the exon structure of NM_007294.4. Select a row to find it on the plot.
BRCA1NM_007294.4
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 BRCA1
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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
Allele count data not recorded
gnomAD v2.1
Allele count data not recorded
Statements
gnomAD v4.1
Absent from gnomAD v4.1.
gnomAD v2.1
Absent from gnomAD v2.1.
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
PP3 SupportingThis variant is a missense substitution within the BRCA1 BRCT repeat domain, a clinically important functional domain spanning amino acids 1650-1857. The bioinformatic dataset reports BayesDel no-AF approximately 0.386-0.39, which is above the ENIGMA PP3 threshold of ≥0.28, and SpliceAI max delta score is 0.03, below the splice-impact threshold of ≥0.2. These findings support a deleterious protein effect without predicted splicing impact, meeting PP3 at Supporting strength. Details ▾Hide ▴
Rule
Apply PP3 for missense variants inside a clinically important functional domain with predicted protein impact, BayesDel no-AF ≥0.28; apply PP3 for predicted splicing when SpliceAI ≥0.2.
Evidence considered
- Supplementary bioinformatic tables: c.5090G>A p.Cys1697Tyr in BRCT repeats
- BayesDel no-AF 0.386406/0.39
- SpliceAI max delta 0.03.
Sources
vcep_s_u_p_p_l_e_m_e_n_t_a_r_y_t_a_b_l_e_s___v_1___2___2_0_2_4___1_1___1_8spliceai ↗cspec ↗vcep_a_p_p_e_n_d_i_c_e_s___v_1___2___2_0_2_4___1_1___1_8
BP4 This variant is inside a clinically important BRCA1 functional domain and has BayesDel no-AF approximately 0.386-0.39, which is above the benign BP4 threshold of ≤0.15. Although SpliceAI max delta score is 0.03 and therefore below the no-splice-impact threshold of ≤0.1, the protein-impact prediction does not support BP4. BP4 is not met. Details ▾Hide ▴
Rule
For missense variants inside a clinically important functional domain, BP4 requires BayesDel no-AF ≤0.15 and SpliceAI ≤0.1.
Evidence considered
- BayesDel no-AF 0.386406/0.39
- SpliceAI max delta 0.03.
Sources
BP7 N/AThis variant is a missense substitution within a clinically important BRCA1 functional domain. BP7 is intended for qualifying benign mRNA-only evidence in intronic, synonymous, or missense/in-frame variants outside clinically important domains, or for domain missense variants only when BS3 is also met; BS3 is not met. BP7 is therefore not applicable. Details ▾Hide ▴
Rule
BP7 applies to well-established mRNA-only evidence showing no damaging effect in specified variant contexts; domain missense variants require BS3 eligibility.
Evidence considered
- SpliceAI max delta 0.03 indicates no predicted splice impact
- but no qualifying benign mRNA-only assay evidence or BS3 evidence was identified.
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.03).
0 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata.
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
Captured gnomAD v4.1 source record
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Captured SpliceAI source record
Open source ↗
ClinVar
Captured ClinVar source record
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/1530970787
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/37635/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/17-41215953-C-T?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr17-43063936-C-T?dataset=gn…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_007294.4%3Ac.5090…
- OncoKB ↗www.oncokb.org/gene/BRCA1/C1697Y
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=BRCA1+c.5090G%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
Absent from gnomAD v4.1.
gnomAD v2.1
Absent from gnomAD v2.1.
ClinVar
This variant has been reported in ClinVar as Likely pathogenic (3 clinical laboratories) and as Pathogenic (3 clinical laboratories) and as Uncertain significance (3 clinical laboratories) and as Likely Pathogenic by ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel, ClinGen (expert panel).
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.03).
Functional
OncoKB has not reviewed this specific variant; no variant-level oncogenicity or biological effect is available. Gene-level context: BRCA1, 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.