About BRCA1
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
BRCA1 c.2155A>G, p.(Lys719Glu)
Classification
Benign
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is benign. Select a step to read what it means.
Benign.A 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 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: 0
Benign evidence criteria: 4
Pathogenic criteria applied · 0
No pathogenic criterion marked as applied in the recorded assessment.
Benign criteria applied · 4
BS1Strong
BS1 · strong
This variant exceeds the ENIGMA BS1 strong threshold for population frequency. The highest observed grpmax FAF is 0.00062195 in gnomAD v2.1 and 0.00068503 in gnomAD v4.1, both above the BS1 strong cutoff of 0.0001 and below the BA1 cutoff of 0.001.
BP1Strong
BP1 · strong
This missense variant is outside the BRCA1 clinically important functional domains used by ENIGMA, and SpliceAI predicts no splice effect with a maximum delta score of 0.00, which is below the BP1 splice threshold of 0.10. These findings meet BP1_Strong.
BP5Strong
BP5 · strong
The BRCA1 clinical-history likelihood ratio for this variant is 0.0137 from 10 probands, which is below the BP5_Strong threshold of 0.05. This provides strong evidence against pathogenicity under the ENIGMA multifactorial clinical-data framework.
BP6Supporting
BP6 · supporting
Expert panel ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel, ClinGen classified as Benign.
Recorded classification: Benign
ENIGMA BRCA1/BRCA2 Specification v1.2 Table 3 final-classification framework (CSPEC/VCEP official framework override).
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
67 / 1,614,060 alleles
gnomAD v4.1: 67 / 1,614,060 alleles. Recorded AF 4.15102e-05. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 7.0823e-05; MAF= 0.00708%, 20/282394 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000803277; MAF= 0.08033%, 20/24898 alleles, homozygotes = 0); grpmax FAF= 0.00062195.
No screenshot for this evidence
Computational predictions
Not recorded
No SpliceAI or REVEL score is recorded in the fields used for this tile.
No listed criterion applied
ClinVar submissions
Not recorded
A ClinVar laboratory submission summary was not recorded.
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.
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 · 6 not met · 9 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.2155A>G (p.Lys719Glu; p.K719E) variant has been reported in ClinVar, where the ClinGen ENIGMA BRCA1 and BRCA2 expert panel classified it as benign.
This variant is present in gnomAD v2.1 and v4.1, with grpmax filter allele frequencies of 0.00062195 and 0.00068503, respectively, both above the ENIGMA BS1 strong threshold of 0.0001 and below the BA1 threshold of 0.001.
A BRCA1 clinical-history likelihood ratio of 0.0137 from 10 probands is below the ENIGMA BP5_Strong threshold of 0.05, supporting evidence against pathogenicity.
No variant-specific damaging or benign functional result for c.2155A>G (p.Lys719Glu) was identified in the reviewed ENIGMA functional assay resources, so PS3 and BS3 were not assessed.
The p.Lys719Glu change lies outside the BRCA1 RING, coiled-coil, and BRCT domains defined by ENIGMA, and SpliceAI predicts no splice impact with a maximum delta score of 0.00, supporting BP1_Strong and not supporting PP3.
No criteria match.
Met · 4
BS1 StrongThis variant exceeds the ENIGMA BS1 strong threshold for population frequency. The highest observed grpmax FAF is 0.00062195 in gnomAD v2.1 and 0.00068503 in gnomAD v4.1, both above the BS1 strong cutoff of 0.0001 and below the BA1 cutoff of 0.001. Details ▾Hide ▴
Rule
ENIGMA BRCA1 BS1_Strong applies when FAF >0.0001 and BS1_Supporting applies when FAF >0.00002 and ≤0.0001.
Evidence considered
- gnomAD v2.1 grpmax FAF = 0.00062195 in African/African American individuals.
- gnomAD v4.1 grpmax FAF = 0.00068503 in African/African American individuals.
Sources
BP1 StrongThis missense variant is outside the BRCA1 clinically important functional domains used by ENIGMA, and SpliceAI predicts no splice effect with a maximum delta score of 0.00, which is below the BP1 splice threshold of 0.10. These findings meet BP1_Strong. Details ▾Hide ▴
Rule
ENIGMA BRCA1 BP1_Strong applies to missense variants outside defined clinically important domains with SpliceAI ≤0.10.
Evidence considered
- Protein change is p.(Lys719Glu) at amino acid 719.
- BRCA1 clinically important domains are aa 2-101
- 1391-1424
- and 1650-1857.
- SpliceAI max delta score = 0.00.
Sources
BP5 StrongThe BRCA1 clinical-history likelihood ratio for this variant is 0.0137 from 10 probands, which is below the BP5_Strong threshold of 0.05. This provides strong evidence against pathogenicity under the ENIGMA multifactorial clinical-data framework. Details ▾Hide ▴
Rule
ENIGMA BRCA1 BP5_Supporting applies at LR ≤0.48, BP5_Moderate at LR ≤0.23, and BP5_Strong at LR ≤0.05.
Evidence considered
- BRCA1 c.2155A>G clinical-history LR = 0.01373116940682096.
- N_Probands = 10.
Sources
BP6 SupportingExpert panel ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel, ClinGen classified as Benign. Details ▾Hide ▴
Not met · 6 · evaluated, threshold not reached
PVS1 This missense variant does not fall into the BRCA1 loss-of-function categories used for PVS1. It is not a nonsense, frameshift, initiation-codon, canonical ±1,2 splice-site, or exon-level deletion/duplication variant, so PVS1 is not met. Details ▾Hide ▴
Rule
ENIGMA BRCA1 PVS1 applies to null variants or qualifying RNA evidence at the appropriate strength.
Evidence considered
- BRCA1 loss of function is an established disease mechanism in the ENIGMA specification.
- NM_007294.4:c.2155A>G is a missense variant encoding p.(Lys719Glu).
- The generic PVS1 scaffold states this variant is outside the default null-variant buckets.
Sources
PM1 This variant is outside the BRCA1 clinically important functional domains defined by ENIGMA, and no hotspot evidence was identified. The affected residue is Lys719, which is outside the RING domain (aa 2-101), coiled-coil domain (aa 1391-1424), and BRCT repeats (aa 1650-1857), so PM1 is not met. Details ▾Hide ▴
Rule
PM1 is not applicable in the BRCA1 ENIGMA specification outside defined clinically important domains.
Evidence considered
- Protein change is p.(Lys719Glu).
- ENIGMA defines BRCA1 clinically important domains as aa 2-101
- 1391-1424
- and 1650-1857.
- Cancer Hotspots did not identify a statistically significant hotspot at this residue.
Sources
PM2 This variant is not absent from population databases. It is present in gnomAD v2.1 at AF 0.0000708 (20/282394 alleles) and in gnomAD v4.1 at AF 0.0000415 (67/1614060 alleles), so the ENIGMA PM2 absence threshold is not met. Details ▾Hide ▴
Rule
ENIGMA BRCA1 PM2_Supporting requires absence from gnomAD controls with adequate coverage.
Evidence considered
- gnomAD v2.1 total AF 0.000070823 with 20/282394 alleles.
- gnomAD v4.1 total AF 0.0000415102 with 67/1614060 alleles.
Sources
PP3 Available predictive evidence does not meet the ENIGMA PP3 thresholds. The variant lies outside the BRCA1 clinically important domains used for missense PP3, and SpliceAI shows no predicted splice effect with a maximum delta score of 0.00, which is below the PP3 splice threshold of 0.20. Details ▾Hide ▴
Rule
ENIGMA BRCA1 PP3 requires BayesDel no-AF ≥0.28 for missense variants inside defined domains or SpliceAI ≥0.20 for predicted splice impact.
Evidence considered
- Protein change is p.(Lys719Glu) at amino acid 719
- outside BRCA1 domains aa 2-101
- 1391-1424
- and 1650-1857.
- SpliceAI max delta score is 0.00.
Still missing
- No qualifying ENIGMA PP3 protein-prediction evidence was identified for this variant.
Sources
PP4 The available BRCA1 clinical-history likelihood ratio is 0.0137 from 10 probands, which is well below the PP4 pathogenic threshold of 2.08. This evidence does not support PP4. Details ▾Hide ▴
Rule
ENIGMA BRCA1 PP4 requires a clinical-data LR ≥2.08 for Supporting, ≥4.3 for Moderate, or ≥18.7 for Strong.
Evidence considered
- BRCA1 c.2155A>G clinical-history LR = 0.01373116940682096.
- N_Probands = 10.
Sources
BA1 The filter allele frequency does not reach the ENIGMA BA1 threshold. The highest observed grpmax FAF is 0.00062195 in gnomAD v2.1 and 0.00068503 in gnomAD v4.1, both below the BA1 cutoff of 0.001. Details ▾Hide ▴
Rule
ENIGMA BRCA1 BA1 requires FAF >0.001 in a non-founder population.
Evidence considered
- gnomAD v2.1 grpmax FAF = 0.00062195.
- gnomAD v4.1 grpmax FAF = 0.00068503.
Sources
Not assessed · 9 · no assessment recorded
PS1 No previously classified pathogenic or likely pathogenic variant with the same established amino acid or splice effect was identified in the reviewed evidence, so PS1 was not assessed. Details ▾Hide ▴
Rule
ENIGMA BRCA1 PS1 requires the same established protein or splice effect as a previously classified pathogenic or likely pathogenic variant.
Evidence considered
- ENIGMA BRCA1 applies PS1 only when the same protein or splice effect has already been established by a pathogenic reference variant.
Still missing
- No variant-specific PS1 reference match was identified in the reviewed materials.
Sources
cspec ↗vcep_specifications_v1_2_2024_11_18
PS3 No variant-specific damaging functional result for c.2155A>G (p.Lys719Glu) was identified in the reviewed ENIGMA functional resources, so PS3 was not assessed. Details ▾Hide ▴
Rule
ENIGMA BRCA1 PS3 requires well-established damaging functional evidence.
Evidence considered
- No c.2155A>G or p.(Lys719Glu) match was found in the reviewed Table 9 functional lookup.
- No c.2155A>G or p.(Lys719Glu) match was found in the reviewed supplementary functional datasets.
Still missing
- No qualifying variant-specific damaging protein or combined mRNA/protein assay result was identified.
Sources
PS4 No case-control study or quantitative prevalence analysis showing a significant enrichment of this variant in affected individuals was identified, so PS4 was not assessed. Details ▾Hide ▴
Rule
ENIGMA BRCA1 PS4 requires case-control evidence with p-value ≤0.05 and OR ≥4 with the lower confidence interval excluding 2.0.
Evidence considered
- ENIGMA BRCA1 PS4 requires significant enrichment in affected individuals compared with controls.
Still missing
- No qualifying odds ratio or case-control dataset was identified for this variant.
Sources
PM3 No evidence was identified that this variant was observed in trans with another BRCA1 variant in an individual with BRCA1-related Fanconi anemia, so PM3 was not assessed. Details ▾Hide ▴
Rule
ENIGMA BRCA1 PM3 applies only to qualifying BRCA1-related Fanconi anemia observations.
Evidence considered
- ENIGMA BRCA1 PM3 is reserved for recessive Fanconi anemia presentations with a points-based framework.
Still missing
- No qualifying Fanconi anemia trans-observation data were identified.
Sources
PP1 No quantitative co-segregation data were identified for this variant, so PP1 was not assessed. Details ▾Hide ▴
Rule
ENIGMA BRCA1 PP1 requires co-segregation with disease using a quantitative LR framework.
Evidence considered
- ENIGMA BRCA1 PP1 requires a quantitative segregation likelihood ratio.
Still missing
- No pedigree-based segregation likelihood ratio was identified.
Sources
BS2 No qualifying observations in unaffected individuals were identified for the ENIGMA BRCA1 BS2 points-based framework, so BS2 was not assessed. Details ▾Hide ▴
Rule
ENIGMA BRCA1 BS2 requires sufficient qualifying points from unaffected observations.
Evidence considered
- ENIGMA BRCA1 BS2 uses a points-based framework tied to absence of Fanconi anemia features.
Still missing
- No qualifying unaffected-observation points data were identified.
Sources
BS3 No variant-specific benign functional result for c.2155A>G (p.Lys719Glu) was identified in the reviewed ENIGMA functional resources, so BS3 was not assessed. Details ▾Hide ▴
Rule
ENIGMA BRCA1 BS3 requires well-established neutral functional evidence.
Evidence considered
- No c.2155A>G or p.(Lys719Glu) match was found in the reviewed Table 9 functional lookup.
- No c.2155A>G or p.(Lys719Glu) match was found in the reviewed supplementary functional datasets.
Still missing
- No qualifying variant-specific neutral protein or combined mRNA/protein assay result was identified.
Sources
BS4 No quantitative lack-of-segregation data were identified for this variant, so BS4 was not assessed. Details ▾Hide ▴
Rule
ENIGMA BRCA1 BS4 requires lack of segregation using a quantitative LR framework.
Evidence considered
- ENIGMA BRCA1 BS4 requires a quantitative segregation likelihood ratio in the benign direction.
Still missing
- No pedigree-based non-segregation likelihood ratio was identified.
Sources
BP7 No qualifying RNA study showing no damaging effect on transcript processing was identified for this missense variant, so BP7 was not assessed. Details ▾Hide ▴
Rule
ENIGMA BRCA1 BP7 requires qualifying RNA or specific silent/intronic evidence under the BRCA1 flowchart.
Evidence considered
- SpliceAI predicts no splice effect with a maximum delta score of 0.00.
- No variant-specific RNA assay match for c.2155A>G was identified in the reviewed splicing reference tables.
Still missing
- No variant-specific RNA assay result demonstrating no splice effect was identified.
Sources
Not applicable · 9· recorded as not applicable Show reasons ▾Hide reasons ▴
PS2 N/APS2 is not applied in the BRCA1 ENIGMA specification. Details ▾Hide ▴
Rule
Not applicable in the BRCA1 ENIGMA specification.
Evidence considered
- The ENIGMA BRCA1 specification marks PS2 as not applicable.
Sources
PM4 N/APM4 is not applied in the BRCA1 ENIGMA specification. Details ▾Hide ▴
Rule
Not applicable in the BRCA1 ENIGMA specification.
Evidence considered
- The ENIGMA BRCA1 specification marks PM4 as not applicable.
Sources
PM5 N/AUnder the BRCA1 ENIGMA specification, PM5 is used for protein-truncating variants in exons where a different proven pathogenic truncating variant has already been observed. This variant is missense, so PM5 is not applicable. Details ▾Hide ▴
Rule
ENIGMA BRCA1 PM5 applies to qualifying protein termination codon variants by exon.
Evidence considered
- NM_007294.4:c.2155A>G is a missense variant encoding p.(Lys719Glu).
- BRCA1 ENIGMA PM5 is specified for PTC variants rather than missense same-codon substitution use.
Sources
PM6 N/APM6 is not applied in the BRCA1 ENIGMA specification. Details ▾Hide ▴
Rule
Not applicable in the BRCA1 ENIGMA specification.
Evidence considered
- The ENIGMA BRCA1 specification marks PM6 as not applicable.
Sources
PP2 N/APP2 is not applied in the BRCA1 ENIGMA specification. Details ▾Hide ▴
Rule
Not applicable in the BRCA1 ENIGMA specification.
Evidence considered
- The ENIGMA BRCA1 specification marks PP2 as not applicable.
Sources
PP5 N/APP5 is not applied in the BRCA1 ENIGMA specification. Details ▾Hide ▴
Rule
Not applicable in the BRCA1 ENIGMA specification.
Evidence considered
- The ENIGMA BRCA1 specification marks PP5 as not applicable.
Sources
BP2 N/ABP2 is not applied in the BRCA1 ENIGMA specification. Details ▾Hide ▴
Rule
Not applicable in the BRCA1 ENIGMA specification.
Evidence considered
- The ENIGMA BRCA1 specification marks BP2 as not applicable.
Sources
BP3 N/ABP3 is not applied in the BRCA1 ENIGMA specification. Details ▾Hide ▴
Rule
Not applicable in the BRCA1 ENIGMA specification.
Evidence considered
- The ENIGMA BRCA1 specification marks BP3 as not applicable.
Sources
BP4 N/AThis missense variant is outside the BRCA1 domain and variant classes for which ENIGMA applies BP4. Under the BRCA1 specification, missense variants outside clinically important domains are evaluated with BP1 rather than BP4 when splicing is not predicted to be affected. Details ▾Hide ▴
Rule
ENIGMA BRCA1 BP4 applies to missense variants inside defined domains with BayesDel no-AF ≤0.15 and SpliceAI ≤0.10, to silent variants inside domains, or to noncanonical intronic variants without predicted splice impact.
Evidence considered
- Protein change is p.(Lys719Glu) at amino acid 719
- outside ENIGMA-defined BRCA1 domains.
- SpliceAI max delta score = 0.00.
Sources
Identifiers
- Gene
- BRCA1
- Transcript
- NM_007294.4
- Coding (HGVS c.)
- NM_007294.4:c.2155A>G
- Protein (HGVS p.)
- NP_009225.1:p.(Lys719Glu)
- GRCh38
- chr17:43093376 T>C
- GRCh37
- chr17:41245393 T>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
—
Transcript span
—
Strand
—
Variants mapped
—
Source
UCSC ncbiRefSeqCurated
All variants in BRCA1
—
Select a row to find it on the plot; use the link to open its page.
| Protein | Location | Classification | Link |
|---|
gnomAD v4.1
67 / 1,614,060 alleles
AF 4.15e-05 · 0 homozygotes · FAF 0.000685
gnomAD v2.1
20 / 282,394 alleles
AF 7.08e-05 · 0 homozygotes · FAF 0.000622
By genetic ancestry
gnomAD v4.1
AF 4.2e-05 · 67 / 1,614,060 alleles · 0 hom · FAF 0.00069
| African/African American64 / 75,066 | 0.00085 |
| Remaining individuals3 / 62,506 | 4.8e-05 |
0 alternate alleles recorded in 8 other groups: Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish, European (non-Finnish).
gnomAD v2.1
AF 7.1e-05 · 20 / 282,394 alleles · 0 hom · FAF 0.00062
| African/African American20 / 24,898 | 0.0008 |
0 alternate alleles recorded in 7 other groups: Admixed American, Ashkenazi Jewish, East Asian, European (Finnish), European (non-Finnish), Remaining individuals, South Asian.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 4.15102e-05; MAF= 0.00415%, 67/1614060 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000852583; MAF= 0.08526%, 64/75066 alleles, homozygotes = 0); grpmax FAF= 0.00068503.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 7.0823e-05; MAF= 0.00708%, 20/282394 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000803277; MAF= 0.08033%, 20/24898 alleles, homozygotes = 0); grpmax FAF= 0.00062195.
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
PP3 Available predictive evidence does not meet the ENIGMA PP3 thresholds. The variant lies outside the BRCA1 clinically important domains used for missense PP3, and SpliceAI shows no predicted splice effect with a maximum delta score of 0.00, which is below the PP3 splice threshold of 0.20. Details ▾Hide ▴
Rule
ENIGMA BRCA1 PP3 requires BayesDel no-AF ≥0.28 for missense variants inside defined domains or SpliceAI ≥0.20 for predicted splice impact.
Evidence considered
- Protein change is p.(Lys719Glu) at amino acid 719
- outside BRCA1 domains aa 2-101
- 1391-1424
- and 1650-1857.
- SpliceAI max delta score is 0.00.
Still missing
- No qualifying ENIGMA PP3 protein-prediction evidence was identified for this variant.
Sources
BP7 No qualifying RNA study showing no damaging effect on transcript processing was identified for this missense variant, so BP7 was not assessed. Details ▾Hide ▴
Rule
ENIGMA BRCA1 BP7 requires qualifying RNA or specific silent/intronic evidence under the BRCA1 flowchart.
Evidence considered
- SpliceAI predicts no splice effect with a maximum delta score of 0.00.
- No variant-specific RNA assay match for c.2155A>G was identified in the reviewed splicing reference tables.
Still missing
- No variant-specific RNA assay result demonstrating no splice effect was identified.
Sources
BP4 N/AThis missense variant is outside the BRCA1 domain and variant classes for which ENIGMA applies BP4. Under the BRCA1 specification, missense variants outside clinically important domains are evaluated with BP1 rather than BP4 when splicing is not predicted to be affected. Details ▾Hide ▴
Rule
ENIGMA BRCA1 BP4 applies to missense variants inside defined domains with BayesDel no-AF ≤0.15 and SpliceAI ≤0.10, to silent variants inside domains, or to noncanonical intronic variants without predicted splice impact.
Evidence considered
- Protein change is p.(Lys719Glu) at amino acid 719
- outside ENIGMA-defined BRCA1 domains.
- SpliceAI max delta score = 0.00.
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
67 / 1,614,060 recorded alleles
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/37452/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/17-41245393-T-C?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr17-43093376-T-C?dataset=gn…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_007294.4%3Ac.2155…
- OncoKB ↗www.oncokb.org/gene/BRCA1/K719E
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=BRCA1+c.2155A%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
This variant is present in gnomAD v4.1 (AF= 4.15102e-05; MAF= 0.00415%, 67/1614060 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000852583; MAF= 0.08526%, 64/75066 alleles, homozygotes = 0); grpmax FAF= 0.00068503.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 7.0823e-05; MAF= 0.00708%, 20/282394 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000803277; MAF= 0.08033%, 20/24898 alleles, homozygotes = 0); grpmax FAF= 0.00062195.
ClinVar
This variant has been reported in ClinVar as Uncertain significance (7 clinical laboratories) and as Likely benign (7 clinical laboratories) and as Likely Benign (1 clinical laboratory) and as Benign 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 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.