About BRCA1
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
BRCA1 c.2998_3003del, p.(Glu1000_Glu1001del)
Classification
Likely benign
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is likely benign. Select a step to read what it means.
Likely benign.A likely benign classification under the recorded framework.
In plain language
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.
LYFE Sciences is an AI system, and it can make mistakes.
Criteria may be applied incorrectly, sources may be misread, and a
confident-looking classification can still be wrong.
Double-check every criterion and its underlying evidence
before relying on any call.
01The reasoning
How it was classified
The recorded framework is ClinGen 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: 2
Pathogenic criteria applied · 0
No pathogenic criterion marked as applied in the recorded assessment.
Benign criteria applied · 2
BS1Supporting
BS1 · supporting
ENIGMA BS1_Supporting applies when filter allele frequency (FAF) is above 0.002% (FAF > 0.00002) and ≤ 0.01% (FAF ≤ 0.0001) in gnomAD v2.1 and/or v3.1/v4.1 non-cancer, non-founder populations. The maximum FAF is 4.101e-05 (0.0041%) in gnomAD v4.1, which falls within the BS1_Supporting range (>0.002%, ≤0.01%). The variant is observed in 5/282,204 alleles in v2.1 and 64/1,613,982 alleles in v4.1, with highest frequency in the European (non-Finnish) population (v4.1 NFE AF=0.00517%).
BP1Strong
BP1 · strong
ENIGMA BP1_Strong applies to in-frame deletions outside a clinically important functional domain with no splicing predicted (SpliceAI ≤ 0.1). The p.Glu1000_Glu1001del deletion is at positions 1000-1001, which is outside the three ENIGMA-defined clinically important functional domains: RING (aa 2-101), coiled-coil (aa 1391-1424), and BRCT (aa 1650-1857). SpliceAI max delta score is 0.01, indicating no predicted splicing impact.
Recorded classification: Likely benign
ENIGMA BRCA1 v1.2.0 Table 3 combination rules. Two benign criteria are met: BP1_Strong (in-frame deletion outside clinically important functional domains with no splicing predicted; SpliceAI max delta=0.01) and BS1_Supporting (FAF 0.0041% in gnomAD v4.1, within >0.002% and ≤0.01% range). No pathogenic criteria are met. 1 Strong (Benign) + 1 Supporting (Benign) satisfies ENIGMA Table 3 Likely Benign combination rule. ENIGMA point system: BP1_Strong (-4) + BS1_Supporting (-1) = -5, which falls in Likely Benign range (-6 to -2).
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
64 / 1,613,982 alleles
gnomAD v4.1: 64 / 1,613,982 alleles. Recorded AF 3.96535e-05. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.77177e-05; MAF= 0.00177%, 5/282204 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 3.88066e-05; MAF= 0.00388%, 5/128844 alleles, homozygotes = 0); grpmax FAF= 1.124e-05.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI score
0.010 maximum delta
Recorded SpliceAI maximum delta score: 0.010. Refer to the recorded PP3/BP4 rationale for interpretation.
No listed criterion applied
SpliceAI ↗
ClinVar submissions
12 reported laboratory submissions
9 Uncertain significance · 3 Likely benign. ClinVar API review status: criteria provided, conflicting classifications.
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. 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
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 BRCA1 VCEP v1.2.0, with the data and sources behind each one.
28 criteria with recorded statuses: 2 met · 14 not met · 0 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
NM_007294.4:c.2998_3003del is an in-frame deletion of 6 nucleotides in BRCA1 exon 10 resulting in deletion of two glutamic acid residues at positions 1000-1001 (p.Glu1000_Glu1001del). This is not a null variant; PVS1 does not apply.
The variant is present in gnomAD at low frequency: 5/282,204 alleles in v2.1 (AF=0.00177%) and 64/1,613,982 alleles in v4.1 (AF=0.00397%), with a maximum filter allele frequency of 0.0041%. This meets ENIGMA BS1_Supporting (FAF >0.002% and ≤0.01%).
The deletion is located at amino acid positions 1000-1001, outside the three ENIGMA-defined clinically important functional domains (RING aa 2-101, coiled-coil aa 1391-1424, BRCT aa 1650-1857). SpliceAI predicts no splicing impact (max delta = 0.01). This meets ENIGMA BP1_Strong for an in-frame deletion outside functional domains with no splicing predicted.
Clinical-history likelihood ratio from Li et al. 2020 (PMID:31853058) is 0.545 based on 7 probands, falling in the neutral zone. Neither PP4 nor BP5 is applied.
The variant was reported as a variant of unknown significance in 1 of 258 ovarian cancer patients by Smith et al. 2001 (PMID:11733976), identified in the RAD51-binding region of BRCA1. This observation alone does not meet any pathogenic criterion threshold.
Overall classification: Likely Benign. Using the ENIGMA point system: BP1_Strong (-4) + BS1_Supporting (-1) = -5 points, which falls in the Likely Benign range (-6 to -2). No pathogenic criteria are met.
No criteria match.
Met · 2
BS1 SupportingENIGMA BS1_Supporting applies when filter allele frequency (FAF) is above 0.002% (FAF > 0.00002) and ≤ 0.01% (FAF ≤ 0.0001) in gnomAD v2.1 and/or v3.1/v4.1 non-cancer, non-founder populations. The maximum FAF is 4.101e-05 (0.0041%) in gnomAD v4.1, which falls within the BS1_Supporting range (>0.002%, ≤0.01%). The variant is observed in 5/282,204 alleles in v2.1 and 64/1,613,982 alleles in v4.1, with highest frequency in the European (non-Finnish) population (v4.1 NFE AF=0.00517%). Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 FAF = 4.101e-05 (0.0041%)
- within BS1_Supporting range (>0.002%
- ≤0.01%)
- gnomAD v2.1 FAF = 1.124e-05 (0.0011%)
- Variant observed across multiple populations in non-founder outbred cohorts
Sources
BP1 StrongENIGMA BP1_Strong applies to in-frame deletions outside a clinically important functional domain with no splicing predicted (SpliceAI ≤ 0.1). The p.Glu1000_Glu1001del deletion is at positions 1000-1001, which is outside the three ENIGMA-defined clinically important functional domains: RING (aa 2-101), coiled-coil (aa 1391-1424), and BRCT (aa 1650-1857). SpliceAI max delta score is 0.01, indicating no predicted splicing impact. Details ▾Hide ▴
Evidence considered
- In-frame deletion at p.E1000_E1001del
- outside RING (2-101)
- coiled-coil (1391-1424)
- and BRCT (1650-1857) domains
- SpliceAI max delta = 0.01
- no splicing impact predicted
Sources
Not met · 14 · evaluated, threshold not reached
PVS1 NM_007294.4:c.2998_3003del is an in-frame 6-bp deletion resulting in p.(Glu1000_Glu1001del). PVS1 under ENIGMA BRCA1 v1.2.0 applies exclusively to null variants (nonsense, frameshift, canonical splice ±1,2, initiation codon, or single/multi-exon deletion). This in-frame deletion does not introduce a premature termination codon or alter the reading frame and is not assigned PVS1 in the ENIGMA Table 4 exon-level decision matrix for BRCA1 exon 10(11). Details ▾Hide ▴
Evidence considered
- In-frame deletion of 6 nucleotides removing Glu1000 and Glu1001
- Not a null variant: no frameshift
- no PTC
- no NMD predicted
- ENIGMA Table 4 does not assign PVS1 to small in-frame deletions within exon 10(11)
Sources
vcep_specifications_table4_v1_2_2024_11_18cspec ↗
PS3 No variant-specific functional evidence demonstrating a damaging effect was identified. ENIGMA Table 9 curated functional assay results are limited to missense and synonymous variants. The variant was not found in the ENIGMA Supplementary Table 4 functional assay dataset. OncoKB reports Unknown Oncogenic Effect with no variant-specific reviewed functional evidence. Details ▾Hide ▴
Evidence considered
- No variant-specific functional assay results in ENIGMA Table 9 or ST4
- OncoKB: Unknown Oncogenic Effect
- no curated functional PMIDs
Still missing
- No functional assay data available for this in-frame deletion
Sources
PS4 ENIGMA PS4 requires case-control study with p≤0.05 and OR≥4 (lower CI excludes 2.0). No case-control data are available for this variant. The variant has been observed in 1 ovarian cancer proband (Smith et al. 2001, PMID:11733976) as a VUS, which is insufficient to meet PS4 thresholds. Details ▾Hide ▴
Evidence considered
- Observed in 1 of 258 ovarian cancer cases as a VUS (PMID:11733976)
- No case-control study available
Still missing
- No case-control data
Sources
PM2 ENIGMA PM2_Supporting requires absence from gnomAD v2.1 (non-cancer, exome only) and gnomAD v3.1/v4.1 (non-cancer). This variant is present in gnomAD: 5/282,204 alleles in v2.1 (AF=0.00177%) and 64/1,613,982 alleles in v4.1 (AF=0.00397%), with highest frequency in European (non-Finnish) population (v4.1 NFE AF=0.00517%). Therefore PM2 is not met. Details ▾Hide ▴
Evidence considered
- Present in gnomAD v2.1: 5/282
- 204 alleles (AF=0.00177%)
- Present in gnomAD v4.1: 64/1
- 613
- 982 alleles (AF=0.00397%)
- grpmax FAF v2.1=1.124e-05
- v4.1=4.101e-05
Sources
PP1 No co-segregation data are available for this variant. ENIGMA PP1 requires quantitative co-segregation analysis with LR≥2.08 for Supporting. Details ▾Hide ▴
Evidence considered
- No co-segregation data identified
Still missing
- No segregation analysis available
Sources
PP3 ENIGMA PP3 requires the variant to be a missense or in-frame insertion/deletion/delins variant inside a clinically important functional domain (RING aa 2-101, coiled-coil aa 1391-1424, or BRCT aa 1650-1857) with BayesDel no-AF score ≥0.28, OR SpliceAI ≥0.2 for splicing prediction. The p.Glu1000_Glu1001del deletion is at positions 1000-1001, which is outside all three ENIGMA-defined functional domains. SpliceAI max delta score is 0.01 (no splicing impact). BayesDel/REVEL are not applicable to non-SNV variants. PP3 is not met. Details ▾Hide ▴
Evidence considered
- In-frame deletion at p.E1000_E1001del
- outside RING (2-101)
- coiled-coil (1391-1424)
- and BRCT (1650-1857) domains
- SpliceAI max delta = 0.01
- no splicing impact predicted
- BayesDel/REVEL not applicable (non-SNV)
Sources
PP4 ENIGMA PP4 is based on clinical-history likelihood ratio from Li et al. 2020 (PMID:31853058). The LR for c.2998_3003delGAGGAA is 0.545 (LOG(LR) = -0.607, N=7 probands), which falls in the neutral zone (>0.48 and <2.08). Per ENIGMA rules, PP4/BP5 is not applied when the LR is in the neutral range. Details ▾Hide ▴
Evidence considered
- Clinical history LR = 0.545 from Li et al. 2020 (N=7 probands)
- Neutral zone: 0.48 < LR < 2.08
- PP4/BP5 not applied
Sources
vcep_pmid_31853058_brca1_clinical_history_lrPMID:31853058 ↗
BA1 ENIGMA BA1 (Stand Alone) requires filter allele frequency (FAF) above 0.1% (FAF > 0.001) in gnomAD v2.1 (non-cancer, exome only) and/or gnomAD v3.1/v4.1 (non-cancer). Maximum FAF is 4.101e-05 (0.0041%) in gnomAD v4.1, well below the 0.1% threshold. Details ▾Hide ▴
Evidence considered
- Max FAF = 4.101e-05 (0.0041%) in gnomAD v4.1
- Well below BA1 threshold of 0.1%
Sources
BS2 ENIGMA BS2 requires observation in a homozygous state, in trans with a pathogenic variant, or in cis with a pathogenic variant in the absence of Fanconi anemia phenotype. No such data are available for this variant. Details ▾Hide ▴
Evidence considered
- No homozygous or compound heterozygous observations identified
- No Fanconi anemia phenotype data
Still missing
- No BS2-qualifying observations
Sources
BS3 No variant-specific well-established functional studies demonstrating no damaging effect on protein function were identified. ENIGMA Table 9 curated functional assay results cover missense and synonymous variants only. The variant was not identified in the ENIGMA Supplementary Table 4 functional assay dataset. Details ▾Hide ▴
Evidence considered
- No functional assay data available for this in-frame deletion
Still missing
- No calibrated functional assay data
Sources
vcep_specifications_table9_v1_2_2024_11_18vcep_supplementarytables_v1_2_2024_11_18
BS4 No segregation data are available to assess lack of segregation. ENIGMA BS4 requires quantitative co-segregation analysis with LR ≤ 0.48 for Supporting. Details ▾Hide ▴
Evidence considered
- No segregation data identified
Still missing
- No segregation analysis available
Sources
BP4 ENIGMA BP4 requires the variant to be a missense or in-frame insertion/deletion/delins variant inside a clinically important functional domain with no predicted impact (BayesDel ≤ 0.15 and SpliceAI ≤ 0.1). The p.Glu1000_Glu1001del deletion is outside the ENIGMA-defined functional domains (RING, coiled-coil, BRCT), so BP4 is not applicable. Details ▾Hide ▴
Evidence considered
- Variant is outside all ENIGMA clinically important functional domains
- SpliceAI max delta = 0.01
Sources
BP5 ENIGMA BP5 is based on clinical-history likelihood ratio from Li et al. 2020 (PMID:31853058). The LR for c.2998_3003delGAGGAA is 0.545, which falls in the neutral zone (>0.48 and <2.08). Per ENIGMA rules, PP4/BP5 is not applied when the LR is in the neutral range. Details ▾Hide ▴
Evidence considered
- Clinical history LR = 0.545 (N=7 probands)
- neutral zone
Sources
vcep_pmid_31853058_brca1_clinical_history_lrPMID:31853058 ↗
BP7 ENIGMA BP7_Strong (RNA) requires well-established in vitro/in vivo functional studies showing no damaging effect as measured by mRNA transcript profile. BP7_Supporting applies to silent variants inside functional domains or intronic variants outside conserved splice motifs. This is an in-frame deletion with no mRNA assay data available, and it does not qualify for BP7_Supporting (not a silent or intronic variant). Details ▾Hide ▴
Evidence considered
- No mRNA functional assay data available
- Not a silent or intronic variant
- BP7_Supporting criteria not met
Still missing
- No mRNA transcript profile data
Sources
Not applicable · 12· recorded as not applicable Show reasons ▾Hide reasons ▴
PS1 N/APS1 under ENIGMA addresses predicted missense substitutions or splicing variants with same impact as a known pathogenic variant. This is an in-frame deletion, not a missense substitution or splicing variant. Details ▾Hide ▴
PS2 VCEPPS2 is Not Applicable under ENIGMA BRCA1 v1.2.0. Details ▾Hide ▴
Sources
PM1 VCEPPM1 is Not Applicable under ENIGMA BRCA1 v1.2.0. Captured by bioinformatic tool prediction and domain analysis per CSPEC. Details ▾Hide ▴
Sources
PM4 VCEPPM4 is Not Applicable under ENIGMA BRCA1 v1.2.0. Details ▾Hide ▴
Sources
PM5 N/AUnder ENIGMA BRCA1 v1.2.0, PM5 is repurposed for protein termination codon (PTC) variants in an exon where a proven pathogenic PTC has been seen before (PM5_PTC). This variant is an in-frame deletion, not a PTC, and does not introduce a stop codon. Classic same-residue missense PM5 is not applicable to deletions. Details ▾Hide ▴
Evidence considered
- In-frame deletion
- not a PTC variant
- ENIGMA PM5 is exclusively for PTC variants
- exon 10(11) has PM5_Strong (PTC) for PTC variants only
Sources
vcep_specifications_table4_v1_2_2024_11_18cspec ↗
PM6 VCEPPM6 is Not Applicable under ENIGMA BRCA1 v1.2.0. Details ▾Hide ▴
Sources
PP2 VCEPPP2 is Not Applicable under ENIGMA BRCA1 v1.2.0. Details ▾Hide ▴
Sources
PP5 VCEPPP5 is Not Applicable under ENIGMA BRCA1 v1.2.0. Details ▾Hide ▴
Sources
BP2 VCEPBP2 is Not Applicable under ENIGMA BRCA1 v1.2.0. Details ▾Hide ▴
Sources
BP3 VCEPBP3 is Not Applicable under ENIGMA BRCA1 v1.2.0. Captured by bioinformatic tool prediction and domain analysis. Details ▾Hide ▴
Sources
BP6 VCEPBP6 is Not Applicable under ENIGMA BRCA1 v1.2.0. Details ▾Hide ▴
Sources
PS5 N/APS5 is not a standard ACMG/AMP criterion and is not defined in the ENIGMA BRCA1 v1.2.0 specification. Details ▾Hide ▴
No further detail was recorded.
Identifiers
- Gene
- BRCA1
- Transcript
- NM_007294.4
- Coding (HGVS c.)
- NM_007294.4:c.2998_3003del
- Protein (HGVS p.)
- NP_009225.1:p.(Glu1000_Glu1001del)
- GRCh38
- chr17:43092527 TTTCCTC>T
- GRCh37
- chr17:41244544 TTTCCTC>T
- ClinVar
- 54743
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
64 / 1,613,982 alleles
AF 3.97e-05 · 0 homozygotes · FAF 4.1e-05
gnomAD v2.1
5 / 282,204 alleles
AF 1.77e-05 · 0 homozygotes · FAF 1.12e-05
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 4e-05 · 64 / 1,613,982 alleles · 0 hom · FAF 4.1e-05
| European (non-Finnish)61 / 1,180,004 | 5.2e-05 |
| African/African American2 / 74,926 | 2.7e-05 |
| Remaining individuals1 / 62,488 | 1.6e-05 |
0 alternate alleles recorded in 7 other groups: Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish.
gnomAD v2.1
AF 1.8e-05 · 5 / 282,204 alleles · 0 hom · FAF 1.1e-05
| European (non-Finnish)5 / 128,844 | 3.9e-05 |
0 alternate alleles recorded in 7 other groups: African/African American, Admixed American, Ashkenazi Jewish, East Asian, European (Finnish), Remaining individuals, South Asian.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 3.96535e-05; MAF= 0.00397%, 64/1613982 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 5.16947e-05; MAF= 0.00517%, 61/1180004 alleles, homozygotes = 0); grpmax FAF= 4.101e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.77177e-05; MAF= 0.00177%, 5/282204 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 3.88066e-05; MAF= 0.00388%, 5/128844 alleles, homozygotes = 0); grpmax FAF= 1.124e-05.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
PP3 ENIGMA PP3 requires the variant to be a missense or in-frame insertion/deletion/delins variant inside a clinically important functional domain (RING aa 2-101, coiled-coil aa 1391-1424, or BRCT aa 1650-1857) with BayesDel no-AF score ≥0.28, OR SpliceAI ≥0.2 for splicing prediction. The p.Glu1000_Glu1001del deletion is at positions 1000-1001, which is outside all three ENIGMA-defined functional domains. SpliceAI max delta score is 0.01 (no splicing impact). BayesDel/REVEL are not applicable to non-SNV variants. PP3 is not met. Details ▾Hide ▴
Evidence considered
- In-frame deletion at p.E1000_E1001del
- outside RING (2-101)
- coiled-coil (1391-1424)
- and BRCT (1650-1857) domains
- SpliceAI max delta = 0.01
- no splicing impact predicted
- BayesDel/REVEL not applicable (non-SNV)
Sources
BP4 ENIGMA BP4 requires the variant to be a missense or in-frame insertion/deletion/delins variant inside a clinically important functional domain with no predicted impact (BayesDel ≤ 0.15 and SpliceAI ≤ 0.1). The p.Glu1000_Glu1001del deletion is outside the ENIGMA-defined functional domains (RING, coiled-coil, BRCT), so BP4 is not applicable. Details ▾Hide ▴
Evidence considered
- Variant is outside all ENIGMA clinically important functional domains
- SpliceAI max delta = 0.01
Sources
BP7 ENIGMA BP7_Strong (RNA) requires well-established in vitro/in vivo functional studies showing no damaging effect as measured by mRNA transcript profile. BP7_Supporting applies to silent variants inside functional domains or intronic variants outside conserved splice motifs. This is an in-frame deletion with no mRNA assay data available, and it does not qualify for BP7_Supporting (not a silent or intronic variant). Details ▾Hide ▴
Evidence considered
- No mRNA functional assay data available
- Not a silent or intronic variant
- BP7_Supporting criteria not met
Still missing
- No mRNA transcript profile data
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01).
9 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata.
Recorded publications
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PMID 25741868 ↗Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.Richards et al. 2015 ACMG/AMP standards and guidelines for sequence variant interpretation. This methodological paper defines the generic ACMG/AMP framework but does not discuss the specific variant NM_007294.4:c.2998_3003del.Does not name this variant
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PMID 26467025 ↗A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.Karbassi et al. 2015 developed a standardized DNA variant scoring system (Sherloc precursor). Discusses variant classification methodology for Mendelian disorders but does not mention NM_007294.4:c.2998_3003del.Does not name this variant
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PMID 27375968 ↗Design and validation of a next generation sequencing assay for hereditary BRCA1 and BRCA2 mutation testing.Kang HP et al. · 2016Kang et al. 2016 describe design and validation of an NGS assay for BRCA1/2 testing. Reports technical validation metrics for the assay but does not discuss NM_007294.4:c.2998_3003del as a specific variant finding.Does not name this variant
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PMID 10359546 ↗Prevalence of BRCA1 and BRCA2 gene mutations in patients with early-onset breast cancer.Peto J et al. · 1999Peto et al. 1999 investigated BRCA1/2 mutation prevalence in 617 early-onset breast cancer patients. Reports gene-level mutation frequencies but does not list NM_007294.4:c.2998_3003del among reported variants.Does not name this variant
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PMID 10923033 ↗The breast cancer information core: database design, structure, and scope.Szabo C et al. · 2000Szabo et al. 2000 describes the Breast Cancer Information Core (BIC) database design and structure for BRCA1/2 mutation cataloging. This database resource paper does not discuss individual variants including NM_007294.4:c.2998_3003del.Does not name this variant
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PMID 11733976 ↗BRCA1 germline mutations and polymorphisms in a clinic-based series of ovarian cancer cases: a Gynecologic Oncology Group study.Smith SA et al. · 2001The variant c.2998_3003del (reported as 3117del6, p.Glu1000_Glu1001del) was identified as a variant of unknown significance in 1 of 258 unselected ovarian cancer patients. The deleted residues are noted as evolutionarily conserved and located in the RAD51-binding domain. The proband had no family history of breast or ovarian cancer.Names this variant
Quoted passage
3117del6 ... Delete E1000–E1001 ... 1 ... No ... Yes ... RAD51-binding
Table 4: BRCA1 Mutations of Unknown Functional Significance
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PMID 12692171 ↗American Society of Clinical Oncology policy statement update: genetic testing for cancer susceptibility.ASCO 2003 policy statement update on genetic testing for cancer susceptibility. Provides clinical practice guidance for cancer genetic testing but does not discuss individual BRCA1/2 variants.Does not name this variant
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PMID 18163131 ↗The emerging landscape of breast cancer susceptibility.Stratton and Rahman 2008 review the landscape of breast cancer susceptibility alleles (high-penetrance, moderate-penetrance, low-penetrance). Discusses BRCA1/BRCA2 at the gene level but does not mention NM_007294.4:c.2998_3003del.Does not name this variant
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PMID 28492532 ↗Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.Nykamp et al. 2017 describe Sherloc, a comprehensive refinement of ACMG-AMP variant classification criteria. Provides an alternative classification framework but does not discuss NM_007294.4:c.2998_3003del.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
64 / 1,613,982 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.010
Open source ↗
ClinVar
9 Uncertain significance · 3 Likely benign
Open source ↗
COSMIC
Captured COSMIC source record
Open source ↗
Cancer hotspots
Captured Cancer Hotspots source record
Open source ↗
OncoKB
Captured OncoKB source record
Open source ↗
ClinGen CSpec
Captured ClinGen CSpec source record
Open source ↗
All source links
- ClinGen CSpec ↗cspec.genome.network/cspec/ui/svi/doc/1530970787
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/54743/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/17-41244544-TTTCCTC-T?dataset…
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr17-43092527-TTTCCTC-T?data…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/17-43092527-TTTCCTC-T
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_007294.4%3Ac.2998…
- OncoKB ↗www.oncokb.org/gene/BRCA1/E1000_E1001del
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=BRCA1+c.2998_3003del
- 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= 3.96535e-05; MAF= 0.00397%, 64/1613982 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 5.16947e-05; MAF= 0.00517%, 61/1180004 alleles, homozygotes = 0); grpmax FAF= 4.101e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.77177e-05; MAF= 0.00177%, 5/282204 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 3.88066e-05; MAF= 0.00388%, 5/128844 alleles, homozygotes = 0); grpmax FAF= 1.124e-05.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Uncertain significance (9 clinical laboratories) and as Likely benign (3 clinical laboratories). (ClinVarID = 54743)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01).
Functional
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. 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.