About BRCA1
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
BRCA1 c.5509T>G, p.(Trp1837Gly)
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 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: 4
Benign evidence criteria: 0
Pathogenic criteria applied · 4
PM2Supporting
PM2 · supporting
This variant is absent from gnomAD v2.1 and gnomAD v4.1. The observed population frequency is 0 in the available gnomAD datasets, which is below the ENIGMA PM2_Supporting absent-from-controls threshold.
PP3Supporting
PP3 · supporting
This missense variant lies in the BRCA1 BRCT repeats, a clinically important functional domain spanning amino acids 1650-1857. The BayesDel no-AF score reported in ENIGMA supplementary bioinformatic data is approximately 0.533, which is above the pathogenic computational threshold of ≥0.28, while SpliceAI max delta score is 0.00; this supports PP3 for predicted protein impact rather than splicing impact.
PP4Moderate
PP4 · moderate
The BRCA1 clinical-history likelihood-ratio table reports this variant in 2 probands with LR 8.0617. This is above the PP4_Moderate threshold of LR ≥4.3 and below the PP4_Strong threshold of LR ≥18.7, supporting PP4 at Moderate strength.
PP5Supporting
PP5 · supporting
Expert panel ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel, ClinGen classified as Pathogenic.
Benign criteria applied · 0
No benign criterion marked as applied in the recorded assessment.
Recorded classification: Uncertain significance
Official ENIGMA BRCA1/BRCA2 v1.2 Table 3 final-classification framework was used. Applied pathogenic evidence comprises PP4_Moderate plus PM2_Supporting, PP3_Supporting, and PP5_Supporting; no benign criteria are applied. This combination does not meet ENIGMA Table 3 thresholds for Pathogenic or Likely Pathogenic, and no benign classification threshold is 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.
Functional evidence
Statement recorded
OncoKB classifies this variant as Likely Oncogenic; biological effect: Likely Loss-of-function.
No listed criterion applied
OncoKB ↗
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: 4 met · 10 not met · 5 not assessed · 9 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.5509T>G (p.Trp1837Gly; W1837G) variant has been reported in ClinVar with an expert-panel Pathogenic classification by the ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel, and OncoKB classifies the variant as Likely Oncogenic with likely loss-of-function biological effect.
This variant is absent from gnomAD v2.1 and gnomAD v4.1, giving an observed population frequency of 0 in the available population datasets and supporting PM2_Supporting under the ENIGMA framework.
ENIGMA curated functional data for c.5509T>G are discordant across calibrated studies, so neither PS3 nor BS3 is met for this variant.
The variant lies in the BRCA1 BRCT repeats and has an ENIGMA supplementary BayesDel no-AF score of approximately 0.533, above the PP3 threshold of ≥0.28, while SpliceAI predicts no significant splice impact with a max delta score of 0.00.
The BRCA1 clinical-history likelihood-ratio table reports c.5509T>G in 2 probands with LR 8.0617, exceeding the PP4_Moderate threshold of LR ≥4.3 and falling below the PP4_Strong threshold of LR ≥18.7.
No criteria match.
Met · 4
PM2 SupportingThis variant is absent from gnomAD v2.1 and gnomAD v4.1. The observed population frequency is 0 in the available gnomAD datasets, which is below the ENIGMA PM2_Supporting absent-from-controls threshold. Details ▾Hide ▴
Rule
ENIGMA BRCA1/2 v1.2 PM2_Supporting: absent from controls in an outbred population in gnomAD datasets, with adequate regional read depth.
Evidence considered
- gnomAD v2.1 search status: absent.
- gnomAD v4.1 search status: absent.
Still missing
- ENIGMA v1.2 specifies gnomAD v2.1 and v3.1 non-cancer datasets with read-depth checks
- the retrieved evidence includes gnomAD v2.1 and v4.1 absence.
Sources
PP3 SupportingThis missense variant lies in the BRCA1 BRCT repeats, a clinically important functional domain spanning amino acids 1650-1857. The BayesDel no-AF score reported in ENIGMA supplementary bioinformatic data is approximately 0.533, which is above the pathogenic computational threshold of ≥0.28, while SpliceAI max delta score is 0.00; this supports PP3 for predicted protein impact rather than splicing impact. Details ▾Hide ▴
Rule
ENIGMA BRCA1/2 v1.2 PP3: missense/in-frame variant inside a clinically important functional domain with BayesDel no-AF ≥0.28, or predicted splicing impact with SpliceAI ≥0.2.
Evidence considered
- BRCA1 p.Trp1837Gly is within the BRCT repeats.
- ENIGMA ST13 lists c.5509T>G p.Trp1837Gly in BRCT repeats with BayesDel no-AF approximately 0.533.
- SpliceAI max delta score is 0.00
- below the splicing pathogenic threshold of ≥0.2.
Sources
PP4 ModerateThe BRCA1 clinical-history likelihood-ratio table reports this variant in 2 probands with LR 8.0617. This is above the PP4_Moderate threshold of LR ≥4.3 and below the PP4_Strong threshold of LR ≥18.7, supporting PP4 at Moderate strength. Details ▾Hide ▴
Rule
ENIGMA BRCA1/2 v1.2 PP4: Supporting LR ≥2.08, Moderate LR ≥4.3, Strong LR ≥18.7, Very Strong LR ≥350.
Evidence considered
- PMID:31853058 BRCA1 clinical-history LR table row for c.5509T>G: N_Probands=2
- LR=8.061718376504666.
Sources
PP5 SupportingExpert panel ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel, ClinGen classified as Pathogenic. Details ▾Hide ▴
Not met · 10 · evaluated, threshold not reached
PVS1 This BRCA1 variant is a missense substitution, p.(Trp1837Gly), and does not create a nonsense, frameshift, initiation-codon, exon-level deletion, or canonical ±1,2 splice variant. Although BRCA1 loss of function is an established disease mechanism, the null-variant PVS1 rule is not met for this missense change. Details ▾Hide ▴
Rule
ENIGMA BRCA1/2 v1.2 PVS1 applies to null variants in genes where loss of function is a known disease mechanism; generic PVS1 scaffold did not identify a qualifying null variant bucket.
Evidence considered
- BRCA1 has official ENIGMA PVS1 guidance and is eligible for PVS1 when an appropriate loss-of-function variant is present.
- NM_007294.4:c.5509T>G is categorized as a non-null missense variant
- NP_009225.1:p.(Trp1837Gly)
- outside the generic PVS1 null-variant buckets.
Sources
PS1 No previously classified pathogenic variant producing the same Trp1837Gly amino acid change, or the same predicted splicing impact, was identified. Other substitutions at this codon are not sufficient for PS1 because they do not produce the same amino acid change. Details ▾Hide ▴
Rule
ENIGMA BRCA1/2 v1.2 PS1 same amino acid change or same predicted splicing impact rule.
Evidence considered
- ENIGMA PS1 requires the same amino acid change or same predicted splicing impact as a previously classified pathogenic variant.
- SpliceAI max delta score is 0.00
- arguing against a predicted splice mechanism.
Sources
PS3 Calibrated functional evidence for c.5509T>G is discordant: two calibrated studies reported a functional effect similar to pathogenic controls, while another reported an intermediate/partial result. ENIGMA Table 9 assigns no PS3 code for this variant, so PS3 is not met. Details ▾Hide ▴
Rule
ENIGMA BRCA1/2 v1.2 PS3 requires well-established calibrated functional studies supportive of a damaging effect; Table 9 provides variant-specific code assignment.
Evidence considered
- Specifications Table 9 row for BRCA1 c.5509T>G p.(Trp1837Gly) assigns code 'None' and states that PS3 and BS3 are not met due to discordant calibrated functional studies.
- Supplementary Table ST4 lists functional impact as complete/partial with conflicting functional evidence.
Sources
vcep_specifications_table9_v1_2_2024_11_18vcep_supplementarytables_v1_2_2024_11_18
BA1 This variant is absent from gnomAD v2.1 and gnomAD v4.1. The observed population frequency is 0, which is below the ENIGMA BA1 threshold of FAF >0.1% (>0.001), so BA1 is not met. Details ▾Hide ▴
Rule
ENIGMA BRCA1/2 v1.2 BA1: 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 gnomAD v2.1 and gnomAD v4.1. The observed population frequency is 0, which is below both ENIGMA BS1 thresholds: >0.002% (>0.00002) for supporting and >0.01% (>0.0001) for strong, so BS1 is not met. Details ▾Hide ▴
Rule
ENIGMA BRCA1/2 v1.2 BS1: Supporting FAF >0.00002 and ≤0.0001; Strong FAF >0.0001 in a non-founder gnomAD population.
Evidence considered
- gnomAD v2.1: absent.
- gnomAD v4.1: absent.
Sources
BS3 Calibrated functional evidence for c.5509T>G is discordant and does not consistently show no damaging effect. ENIGMA Table 9 assigns no BS3 code for this variant, so BS3 is not met. Details ▾Hide ▴
Rule
ENIGMA BRCA1/2 v1.2 BS3 requires calibrated functional studies showing no damaging effect; Table 9 provides variant-specific code assignment.
Evidence considered
- Specifications Table 9 row for BRCA1 c.5509T>G p.(Trp1837Gly) assigns code 'None' and states that PS3 and BS3 are not met due to discordant calibrated functional studies.
Sources
vcep_specifications_table9_v1_2_2024_11_18vcep_supplementarytables_v1_2_2024_11_18
BP1 BP1_Strong applies to missense, silent, or in-frame variants outside clinically important functional domains with no predicted splicing effect. This variant is inside the BRCA1 BRCT repeats, a clinically important functional domain, so BP1 is not met despite SpliceAI max delta score 0.00. Details ▾Hide ▴
Rule
ENIGMA BRCA1/2 v1.2 BP1_Strong: missense/silent/in-frame variant outside clinically important functional domains and SpliceAI ≤0.1.
Evidence considered
- p.Trp1837Gly lies within BRCA1 BRCT repeats
- amino acids 1650-1857.
- SpliceAI max delta score is 0.00.
Sources
BP4 BP4 requires no predicted protein or splicing impact for an in-domain missense variant, including BayesDel no-AF ≤0.15 and SpliceAI ≤0.1. Although SpliceAI max delta score is 0.00, the ENIGMA supplementary BayesDel no-AF score is approximately 0.533, which is above the benign threshold of ≤0.15, so BP4 is not met. Details ▾Hide ▴
Rule
ENIGMA BRCA1/2 v1.2 BP4: in-domain missense/in-frame variants require BayesDel no-AF ≤0.15 and SpliceAI ≤0.1.
Evidence considered
- ENIGMA ST13 lists BayesDel no-AF approximately 0.533 for c.5509T>G.
- SpliceAI max delta score is 0.00.
Sources
BP5 The BRCA1 clinical-history likelihood-ratio table reports LR 8.0617 for this variant, which is above the pathogenic-direction PP4_Moderate threshold and not below the BP5 supporting threshold of LR ≤0.48. Therefore BP5 is not met. Details ▾Hide ▴
Rule
ENIGMA BRCA1/2 v1.2 BP5: Supporting LR ≤0.48, Moderate LR ≤0.23, Strong LR ≤0.05, Very Strong LR ≤0.00285.
Evidence considered
- PMID:31853058 BRCA1 clinical-history LR table row for c.5509T>G: LR=8.061718376504666.
Sources
BP7 BP7 is intended for specific silent, intronic, out-of-domain missense/in-frame, or RNA-assay contexts. This variant is an in-domain BRCA1 BRCT missense variant, and no qualifying benign RNA evidence or BS3 evidence was identified; therefore BP7 is not met. Details ▾Hide ▴
Rule
ENIGMA BRCA1/2 v1.2 BP7: RNA/no-splicing benign evidence in specified variant contexts; in-domain missense variants require BS3 to be eligible for BP7_Strong RNA.
Evidence considered
- The variant is a missense substitution in the BRCT functional domain.
- SpliceAI max delta score is 0.00
- but BP7 eligibility criteria for an in-domain missense variant are not satisfied.
Sources
Not assessed · 5 · no assessment recorded
PS4 No case-control evidence was identified showing that this variant is significantly enriched in affected individuals with p ≤0.05 and odds ratio ≥4 with the lower confidence interval excluding 2.0. Therefore PS4 was not assessed as met. Details ▾Hide ▴
Rule
ENIGMA BRCA1/2 v1.2 PS4 requires significant enrichment in cases versus controls with p ≤0.05 and OR ≥4, lower CI excluding 2.0.
Evidence considered
- ClinVar reports an expert-panel pathogenic classification but does not by itself provide the case-control statistics required for PS4.
Still missing
- Variant-specific case-control odds ratio
- confidence interval
- and p-value were not identified.
Sources
PM3 No Fanconi anemia phenotype or qualifying biallelic BRCA1 co-occurrence evidence was identified. PM3 was therefore not assessed as met. Details ▾Hide ▴
Rule
ENIGMA BRCA1/2 v1.2 PM3 point-based Fanconi anemia/co-occurrence framework.
Evidence considered
- ENIGMA PM3 applies to BRCA1/2-related Fanconi anemia with qualifying co-occurring variants and point-based evidence.
Still missing
- No proband-level phenotype and phase/co-occurrence data were identified.
Sources
PP1 No quantitative co-segregation evidence was identified for this variant. PP1 requires a segregation likelihood ratio of at least 2.08 for supporting strength, and no such LR was available. Details ▾Hide ▴
Rule
ENIGMA BRCA1/2 v1.2 PP1: Supporting LR ≥2.08, Moderate LR ≥4.3, Strong LR ≥18.7, Very Strong LR ≥350.
Evidence considered
- ENIGMA PP1 requires quantitative co-segregation analysis with LR thresholds.
Still missing
- Variant-specific co-segregation likelihood ratio was not identified.
Sources
BS2 No qualifying observation in individuals without features of BRCA1/2-related Fanconi anemia was identified. BS2 requires point-based unaffected-carrier evidence, and no such evidence was available. Details ▾Hide ▴
Rule
ENIGMA BRCA1/2 v1.2 BS2: Supporting 1 point, Moderate 2 points, Strong ≥4 points.
Evidence considered
- ENIGMA BS2 uses a point-based framework for observations in the absence of recessive-disease features.
Still missing
- No qualifying unaffected-carrier data were identified.
Sources
BS4 No quantitative lack-of-segregation evidence was identified for this variant. BS4 requires a segregation likelihood ratio of ≤0.48 for supporting benign evidence, and no such LR was available. Details ▾Hide ▴
Rule
ENIGMA BRCA1/2 v1.2 BS4: Supporting LR ≤0.48, Moderate LR ≤0.23, Strong LR ≤0.05, Very Strong LR ≤0.00285.
Evidence considered
- ENIGMA BS4 requires quantitative co-segregation analysis with LR thresholds.
Still missing
- Variant-specific lack-of-segregation LR was not identified.
Sources
Not applicable · 9· recorded as not applicable Show reasons ▾Hide reasons ▴
PS2 N/ADe novo occurrence is not an applicable ENIGMA BRCA1/2 criterion for this framework. Details ▾Hide ▴
Rule
ENIGMA BRCA1/2 v1.2: PS2 not applicable.
Evidence considered
- CSPEC lists PS2 as not applicable.
Sources
PM1 N/APM1 is not used as an applicable standalone criterion under the ENIGMA BRCA1/2 specification. The BRCT domain location is instead incorporated into the ENIGMA PP3/BP4/BP1 bioinformatic framework. Details ▾Hide ▴
Rule
ENIGMA BRCA1/2 v1.2: PM1 not applicable as a standalone criterion.
Evidence considered
- CSPEC lists PM1 as not applicable.
- BRCA1 BRCT repeats are defined as a clinically important functional domain spanning amino acids 1650-1857.
Sources
cspec ↗vcep_appendices_v1_2_2024_11_18
PM4 N/APM4 is not applicable under the ENIGMA BRCA1/2 specification for this variant interpretation framework. Details ▾Hide ▴
Rule
ENIGMA BRCA1/2 v1.2: PM4 not applicable.
Evidence considered
- CSPEC lists PM4 as not applicable.
Sources
PM5 N/AENIGMA PM5 is applied to protein termination codon variants in exons where a different proven pathogenic protein termination codon variant has been observed. This variant is missense, p.(Trp1837Gly), so PM5_PTC is not applicable. Details ▾Hide ▴
Rule
ENIGMA BRCA1/2 v1.2 PM5_PTC applies to qualifying protein termination codon variants, not missense variants.
Evidence considered
- The variant consequence is missense
- not a protein termination codon variant.
Sources
cspec ↗vcep_specifications_table4_v1_2_2024_11_18
PM6 N/AAssumed de novo occurrence is not an applicable ENIGMA BRCA1/2 criterion for this framework. Details ▾Hide ▴
Rule
ENIGMA BRCA1/2 v1.2: PM6 not applicable.
Evidence considered
- CSPEC lists PM6 as not applicable.
Sources
PP2 N/APP2 is not applicable under the ENIGMA BRCA1/2 specification. Details ▾Hide ▴
Rule
ENIGMA BRCA1/2 v1.2: PP2 not applicable.
Evidence considered
- CSPEC lists PP2 as not applicable.
Sources
BP2 N/ABP2 is not applicable under the ENIGMA BRCA1/2 specification. Details ▾Hide ▴
Rule
ENIGMA BRCA1/2 v1.2: BP2 not applicable.
Evidence considered
- CSPEC lists BP2 as not applicable.
Sources
BP3 N/ABP3 is not applicable under the ENIGMA BRCA1/2 specification. Details ▾Hide ▴
Rule
ENIGMA BRCA1/2 v1.2: BP3 not applicable.
Evidence considered
- CSPEC lists BP3 as not applicable.
Sources
BP6 N/ABP6 is not applicable under the ENIGMA BRCA1/2 specification; benign database assertions are not used as standalone evidence. Details ▾Hide ▴
Rule
ENIGMA BRCA1/2 v1.2: BP6 not applicable.
Evidence considered
- CSPEC lists BP6 as not applicable.
Sources
Identifiers
- Gene
- BRCA1
- Transcript
- NM_007294.4
- Coding (HGVS c.)
- NM_007294.4:c.5509T>G
- Protein (HGVS p.)
- NP_009225.1:p.(Trp1837Gly)
- GRCh38
- chr17:43045761 A>C
- GRCh37
- chr17:41197778 A>C
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 missense variant lies in the BRCA1 BRCT repeats, a clinically important functional domain spanning amino acids 1650-1857. The BayesDel no-AF score reported in ENIGMA supplementary bioinformatic data is approximately 0.533, which is above the pathogenic computational threshold of ≥0.28, while SpliceAI max delta score is 0.00; this supports PP3 for predicted protein impact rather than splicing impact. Details ▾Hide ▴
Rule
ENIGMA BRCA1/2 v1.2 PP3: missense/in-frame variant inside a clinically important functional domain with BayesDel no-AF ≥0.28, or predicted splicing impact with SpliceAI ≥0.2.
Evidence considered
- BRCA1 p.Trp1837Gly is within the BRCT repeats.
- ENIGMA ST13 lists c.5509T>G p.Trp1837Gly in BRCT repeats with BayesDel no-AF approximately 0.533.
- SpliceAI max delta score is 0.00
- below the splicing pathogenic threshold of ≥0.2.
Sources
BP4 BP4 requires no predicted protein or splicing impact for an in-domain missense variant, including BayesDel no-AF ≤0.15 and SpliceAI ≤0.1. Although SpliceAI max delta score is 0.00, the ENIGMA supplementary BayesDel no-AF score is approximately 0.533, which is above the benign threshold of ≤0.15, so BP4 is not met. Details ▾Hide ▴
Rule
ENIGMA BRCA1/2 v1.2 BP4: in-domain missense/in-frame variants require BayesDel no-AF ≤0.15 and SpliceAI ≤0.1.
Evidence considered
- ENIGMA ST13 lists BayesDel no-AF approximately 0.533 for c.5509T>G.
- SpliceAI max delta score is 0.00.
Sources
BP7 BP7 is intended for specific silent, intronic, out-of-domain missense/in-frame, or RNA-assay contexts. This variant is an in-domain BRCA1 BRCT missense variant, and no qualifying benign RNA evidence or BS3 evidence was identified; therefore BP7 is not met. Details ▾Hide ▴
Rule
ENIGMA BRCA1/2 v1.2 BP7: RNA/no-splicing benign evidence in specified variant contexts; in-domain missense variants require BS3 to be eligible for BP7_Strong RNA.
Evidence considered
- The variant is a missense substitution in the BRCT functional domain.
- SpliceAI max delta score is 0.00
- but BP7 eligibility criteria for an in-domain missense variant are not satisfied.
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
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/55607/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/17-41197778-A-C?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr17-43045761-A-C?dataset=gn…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_007294.4%3Ac.5509…
- OncoKB ↗www.oncokb.org/gene/BRCA1/W1837G
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=BRCA1+c.5509T%3EG
- 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 (2 clinical laboratories) and as Pathogenic (2 clinical laboratories) and as Uncertain significance (1 clinical laboratory) and as Likely Pathogenic (1 clinical laboratory) and as 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 = 0.00).
Functional
OncoKB classifies this variant as Likely Oncogenic; biological effect: Likely Loss-of-function.
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.