About BRCA2
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
BRCA2 c.8023A>G, p.(Ile2675Val)
Classification
Pathogenic
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is pathogenic. Select a step to read what it means.
Pathogenic.A 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 BRCA2 VCEP v1.2.0. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.
Recorded applied criteria
The applied criteria and their strengths are shown as assessed under the stated framework.
Pathogenic evidence criteria: 4
Benign evidence criteria: 0
Pathogenic criteria applied · 4
PP1Very strong
PP1 · very strong
This variant shows strong segregation with disease. The quantitative segregation likelihood ratio is 605.14, which is above the ENIGMA PP1_Very Strong threshold of 350.
PP3Supporting
PP3 · supporting
Computational evidence supports a splice-altering effect. SpliceAI predicts a strong splice impact with a maximum delta score of 0.99, which is above the ENIGMA PP3 threshold of 0.2 for predicted splicing impact.
PP4Supporting
PP4 · supporting
Clinical-history evidence is in the pathogenic direction. The family-history likelihood ratio is 2.88, which is above the ENIGMA PP4 threshold of 2.08 and below the moderate threshold of 4.3, supporting PP4 at supporting 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: Pathogenic
ENIGMA BRCA1 and BRCA2 Specification v1.2 Table 3 final-classification framework (CSPEC/VCEP 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
1 / 1,614,050 alleles
gnomAD v4.1: 1 / 1,614,050 alleles. Recorded AF 6.19559e-07. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 3.98286e-06; MAF= 0.00040%, 1/251076 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 5.43833e-05; MAF= 0.00544%, 1/18388 alleles, homozygotes = 0).
No listed criterion applied
SpliceAI score
0.990 maximum delta
Recorded SpliceAI maximum delta score: 0.990. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
17 reported laboratory submissions
14 Pathogenic · 3 Likely pathogenic.
Functional evidence
Statement recorded
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Loss-of-function; curated oncogenicity label: Likely Oncogenic.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
No matching record reported
This variant has not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under ClinGen BRCA2 VCEP v1.2.0, with the data and sources behind each one.
28 criteria with recorded statuses: 4 met · 11 not met · 4 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 BRCA2 c.8023A>G (p.Ile2675Val) variant has not been observed in somatic cancers in COSMIC and has been reported in ClinVar as Pathogenic by the ClinGen ENIGMA BRCA1/2 expert panel.
This variant is present at very low frequency in population databases, with 1/251076 alleles in gnomAD v2.1 and 1/1614050 alleles in gnomAD v4.1, with no homozygotes reported.
In published splice studies summarized in the ENIGMA-aligned BRCA resource, this variant generated a strong donor site within exon 18 and was associated with a predominant exon 18-deleted transcript; the multifactorial dataset also shows a segregation likelihood ratio of 605.14 and an overall posterior probability of pathogenicity of 0.999651.
Computational evidence supports splice disruption, with SpliceAI 0.99 exceeding the BRCA2 ENIGMA PP3 threshold of 0.2; REVEL is high at 0.88, while BayesDel is 0.086 and does not support a benign BP4 call because SpliceAI is above the BP4 threshold of 0.1.
No criteria match.
Met · 4
PP1 Very strongThis variant shows strong segregation with disease. The quantitative segregation likelihood ratio is 605.14, which is above the ENIGMA PP1_Very Strong threshold of 350. Details ▾Hide ▴
Rule
ENIGMA BRCA2 PP1_Very Strong applies when segregation LR is ≥350:1.
Evidence considered
- Segregation LR 605.13969286 for BRCA2 c.8023A>G in the Parsons/Easton multifactorial dataset.
Sources
PP3 SupportingComputational evidence supports a splice-altering effect. SpliceAI predicts a strong splice impact with a maximum delta score of 0.99, which is above the ENIGMA PP3 threshold of 0.2 for predicted splicing impact. Details ▾Hide ▴
Rule
ENIGMA BRCA2 PP3_Supporting applies for predicted splicing impact when SpliceAI is ≥0.2.
Evidence considered
- SpliceAI max delta 0.99.
- REVEL 0.88.
- BayesDel 0.0862004.
Sources
PP4 SupportingClinical-history evidence is in the pathogenic direction. The family-history likelihood ratio is 2.88, which is above the ENIGMA PP4 threshold of 2.08 and below the moderate threshold of 4.3, supporting PP4 at supporting strength. Details ▾Hide ▴
Rule
ENIGMA BRCA2 PP4_Supporting applies for multifactorial clinical data LR ≥2.08 and <4.3.
Evidence considered
- Family history LR 2.8834980449 for BRCA2 c.8023A>G in the multifactorial dataset.
Sources
PP5 SupportingExpert panel ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel, ClinGen classified as Pathogenic. Details ▾Hide ▴
Not met · 11 · evaluated, threshold not reached
PVS1 RNA studies identified a predominant in-frame exon 18 deletion transcript for this variant, but the available evidence does not show a canonical null allele or provide a clear ENIGMA PVS1(RNA) weight for this specific event. Available evidence therefore does not support applying PVS1 at this time. Details ▾Hide ▴
Rule
ENIGMA BRCA2 PVS1/PVS1(RNA) requires an established loss-of-function transcript consequence at an appropriate weight.
Evidence considered
- BRCA2 c.8023A>G is a missense substitution rather than a default null variant.
- Splicing studies reported a predominant in-frame exon 18-deleted transcript for this variant.
Still missing
- Variant-specific ENIGMA PVS1(RNA) weight for the observed exon 18 skipping event was not directly identified in the retrieved materials.
Sources
PS1 No qualifying previously classified pathogenic or likely pathogenic comparator with the same proven protein or splicing consequence was identified for PS1 application. Details ▾Hide ▴
Rule
ENIGMA BRCA2 PS1 requires a previously classified variant with the same relevant protein or splicing consequence.
Evidence considered
- No same-effect pathogenic comparator was identified.
Still missing
- No qualifying PS1 comparator was identified in the retrieved evidence.
Sources
PS3 Published evidence shows abnormal splicing rather than a calibrated protein-function assay result for this variant. Under the BRCA2 ENIGMA specification, mRNA-only damaging evidence is considered under PVS1(RNA) rather than PS3, and no qualifying Table 9 PS3 assignment was identified. Details ▾Hide ▴
Rule
ENIGMA BRCA2 PS3 is reserved for well-established functional studies measuring damaging effect via protein or combined mRNA+protein.
Evidence considered
- No exact variant match was identified in ENIGMA Table 9.
- Available functional evidence is splice/RNA based.
Still missing
- No qualifying ENIGMA Table 9 PS3 entry for this variant was identified.
Sources
vcep_specifications_table9_v1_2_2024_11_18vcep_humu_40_1557_s001PMID:18424508 ↗PMID:22505045 ↗cspec ↗
PM2 This variant is not absent from population databases. It is present in gnomAD v2.1 at 1/251076 alleles (AF 3.98e-06) and in gnomAD v4.1 at 1/1614050 alleles (AF 6.20e-07), so the ENIGMA requirement for absence from controls is not met. Details ▾Hide ▴
Rule
ENIGMA BRCA2 PM2_Supporting requires absence from gnomAD controls with adequate coverage.
Evidence considered
- gnomAD v2.1 total AC/AN 1/251076.
- gnomAD v4.1 total AC/AN 1/1614050.
Sources
BA1 Population frequency does not reach the ENIGMA BA1 threshold. The highest observed population frequency is 5.44e-05 in gnomAD v2.1 East Asian and 2.23e-05 in gnomAD v4.1 East Asian, both below the BA1 threshold of 0.001. Details ▾Hide ▴
Rule
ENIGMA BRCA2 BA1 requires FAF >0.001.
Evidence considered
- Best observed subpopulation AF 5.43833e-05 in gnomAD v2.1 EAS.
- Best observed subpopulation AF 2.22836e-05 in gnomAD v4.1 EAS.
Sources
BS3 Available functional evidence does not show normal or retained function. Instead, RNA studies reported abnormal splicing with exon 18 deletion, and no qualifying benign Table 9 BS3 assignment was identified. Details ▾Hide ▴
Rule
ENIGMA BRCA2 BS3 requires well-established functional studies showing no damaging effect.
Evidence considered
- No exact variant match was identified in ENIGMA Table 9.
- Splicing assays reported exon 18 deletion rather than no effect.
Still missing
- No qualifying ENIGMA Table 9 BS3 entry for this variant was identified.
Sources
BS4 Available segregation evidence is in favor of pathogenicity rather than lack of segregation. The segregation likelihood ratio is 605.14, whereas ENIGMA BS4 requires a likelihood ratio of 0.48 or lower for benign evidence. Details ▾Hide ▴
Rule
ENIGMA BRCA2 BS4 requires quantitative non-segregation evidence, with supporting benign weight at LR ≤0.48.
Evidence considered
- Segregation LR 605.13969286.
Sources
BP1 This missense variant does not meet BRCA2 ENIGMA BP1 because it is not a low-risk missense change without splice concern. SpliceAI predicts strong splice impact with a score of 0.99, which is above the BP1 requirement for no predicted splicing impact at 0.1 or lower. Details ▾Hide ▴
Rule
ENIGMA BRCA2 BP1 requires a missense or silent variant without predicted splicing impact, with SpliceAI ≤0.1.
Evidence considered
- SpliceAI max delta 0.99.
Sources
BP4 Computational evidence does not support BP4. Although the BayesDel score is 0.086 and below the BRCA2 no-impact threshold of 0.18, SpliceAI is 0.99, which is above the BP4 requirement for no predicted splice impact at 0.1 or lower. Details ▾Hide ▴
Rule
ENIGMA BRCA2 BP4 requires no predicted protein or splicing impact, including SpliceAI ≤0.1.
Evidence considered
- BayesDel 0.0862004.
- SpliceAI max delta 0.99.
Sources
BP5 Available clinical-history evidence is not in the benign direction. The family-history likelihood ratio is 2.88, which is above 1 and above the benign BP5 threshold of 0.48. Details ▾Hide ▴
Rule
ENIGMA BRCA2 BP5 applies only when multifactorial clinical data produce LR ≤0.48 against pathogenicity.
Evidence considered
- Family history LR 2.8834980449.
Still missing
- No benign-direction multifactorial clinical-history LR was identified.
Sources
BP7 This is a missense variant with predicted splice impact rather than a synonymous or eligible intronic change with no splice effect, so BP7 is not met. Details ▾Hide ▴
Rule
ENIGMA BRCA2 BP7 is reserved for eligible synonymous or intronic variants, or RNA data showing no damaging splicing effect in the appropriate context.
Evidence considered
- Missense variant.
- SpliceAI max delta 0.99.
Sources
Not assessed · 4 · no assessment recorded
PS4 Multifactorial pathogenic evidence was identified for this variant, but no direct case-control odds ratio with p-value meeting the BRCA2 ENIGMA PS4 threshold was extracted from the retrieved evidence. PS4 was therefore not assessed. Details ▾Hide ▴
Rule
ENIGMA BRCA2 PS4 requires significant case enrichment with p-value ≤0.05 and OR ≥4, with lower confidence interval excluding 2.0.
Evidence considered
- Supplementary resources show pathogenic multifactorial/posterior evidence but not a directly extracted PS4 case-control statistic.
Still missing
- No direct PS4-qualifying case-control OR and p-value were identified.
Sources
PM3 No evidence was identified showing this variant in trans with another pathogenic BRCA2 variant in an individual with a phenotype consistent with BRCA2-related Fanconi anemia. PM3 was not assessed. Details ▾Hide ▴
Rule
ENIGMA BRCA2 PM3 applies only in the Fanconi anemia context with qualifying co-occurrence evidence.
Evidence considered
- No qualifying PM3 proband-level evidence was identified.
Still missing
- No qualifying biallelic BRCA2 Fanconi anemia observations were identified.
Sources
BS1 This variant is present at a very low frequency in gnomAD, but the retrieved data did not provide a qualifying ENIGMA filter allele frequency value for BS1 assessment. BS1 was therefore not assessed. Details ▾Hide ▴
Rule
ENIGMA BRCA2 BS1 depends on non-founder filter allele frequency thresholds.
Evidence considered
- Observed AF is low in both gnomAD v2.1 and v4.1
- but retrieved FAF fields were not populated.
Still missing
- No qualifying non-founder FAF value was identified in the retrieved evidence.
Sources
BS2 No qualifying observations were identified showing this variant in individuals without features of BRCA2-related Fanconi anemia under the ENIGMA BS2 framework. Details ▾Hide ▴
Rule
ENIGMA BRCA2 BS2 is point-based and depends on absence of Fanconi anemia features.
Evidence considered
- No qualifying BS2 evidence was identified.
Still missing
- No qualifying BS2 point-based evidence was identified.
Sources
Not applicable · 9· recorded as not applicable Show reasons ▾Hide reasons ▴
PS2 VCEPThis criterion is not used in the BRCA2 ENIGMA specification. Details ▾Hide ▴
VCEP rule
Not applicable in BRCA2 ENIGMA specifications.
Evidence considered
- PS2 is marked not applicable in the BRCA2 ENIGMA ruleset.
Sources
PM1 VCEPThis criterion is not used in the BRCA2 ENIGMA specification. Details ▾Hide ▴
VCEP rule
Not applicable in BRCA2 ENIGMA specifications.
Evidence considered
- PM1 is marked not applicable in the BRCA2 ENIGMA ruleset.
Sources
PM4 VCEPThis criterion is not used in the BRCA2 ENIGMA specification. Details ▾Hide ▴
VCEP rule
Not applicable in BRCA2 ENIGMA specifications.
Evidence considered
- PM4 is marked not applicable in the BRCA2 ENIGMA ruleset.
Sources
PM5 N/AFor BRCA2 ENIGMA, PM5 is repurposed for truncating or protein-termination-codon logic rather than classic same-residue missense comparison. This missense variant is therefore not eligible for PM5. Details ▾Hide ▴
Rule
ENIGMA BRCA2 PM5 is used for PTC/truncating logic, not classic same-residue missense logic.
Evidence considered
- PM5 candidates artifact designates BRCA2 PM5 as PTC-specific for this case.
Sources
cspec ↗pm5_candidates
PM6 VCEPThis criterion is not used in the BRCA2 ENIGMA specification. Details ▾Hide ▴
VCEP rule
Not applicable in BRCA2 ENIGMA specifications.
Evidence considered
- PM6 is marked not applicable in the BRCA2 ENIGMA ruleset.
Sources
PP2 VCEPThis criterion is not used in the BRCA2 ENIGMA specification. Details ▾Hide ▴
VCEP rule
Not applicable in BRCA2 ENIGMA specifications.
Evidence considered
- PP2 is marked not applicable in the BRCA2 ENIGMA ruleset.
Sources
BP2 VCEPThis criterion is not used in the BRCA2 ENIGMA specification. Details ▾Hide ▴
VCEP rule
Not applicable in BRCA2 ENIGMA specifications.
Evidence considered
- BP2 is marked not applicable in the BRCA2 ENIGMA ruleset.
Sources
BP3 VCEPThis criterion is not used in the BRCA2 ENIGMA specification. Details ▾Hide ▴
VCEP rule
Not applicable in BRCA2 ENIGMA specifications.
Evidence considered
- BP3 is marked not applicable in the BRCA2 ENIGMA ruleset.
Sources
BP6 VCEPThis criterion is not used in the BRCA2 ENIGMA specification. Details ▾Hide ▴
VCEP rule
Not applicable in BRCA2 ENIGMA specifications.
Evidence considered
- BP6 is marked not applicable in the BRCA2 ENIGMA ruleset.
Sources
Identifiers
- Gene
- BRCA2
- Transcript
- NM_000059.3
- Coding (HGVS c.)
- NM_000059.3:c.8023A>G
- Protein (HGVS p.)
- NP_000050.2:p.(Ile2675Val)
- GRCh38
- chr13:32363225 A>G
- GRCh37
- chr13:32937362 A>G
- ClinVar
- 52475
Gene diagram
Every interpreted variant in BRCA2, mapped onto the exon structure of NM_000059.3. Select a row to find it on the plot.
BRCA2NM_000059.3
Fetching transcript structure from UCSC…
Exons
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Transcript span
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Strand
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Variants mapped
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Source
UCSC ncbiRefSeqCurated
All variants in BRCA2
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Select a row to find it on the plot; use the link to open its page.
| Protein | Location | Classification | Link |
|---|
gnomAD v4.1
1 / 1,614,050 alleles
AF 6.2e-07 · 0 homozygotes
gnomAD v2.1
1 / 251,076 alleles
AF 3.98e-06 · 0 homozygotes
By genetic ancestry
gnomAD v4.1
AF 6.2e-07 · 1 / 1,614,050 alleles · 0 hom
| East Asian1 / 44,876 | 2.2e-05 |
0 alternate alleles recorded in 9 other groups: Remaining individuals, Admixed American, European (Finnish), Amish, Middle Eastern, South Asian, Ashkenazi Jewish, African/African American, European (non-Finnish).
gnomAD v2.1
AF 4e-06 · 1 / 251,076 alleles · 0 hom
| East Asian1 / 18,388 | 5.4e-05 |
0 alternate alleles recorded in 7 other groups: African/African American, Admixed American, Ashkenazi Jewish, European (Finnish), European (non-Finnish), Remaining individuals, South Asian.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 6.19559e-07; MAF= 0.00006%, 1/1614050 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 2.22836e-05; MAF= 0.00223%, 1/44876 alleles, homozygotes = 0).
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 3.98286e-06; MAF= 0.00040%, 1/251076 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 5.43833e-05; MAF= 0.00544%, 1/18388 alleles, homozygotes = 0).
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.880
- BayesDel
- 0.086
How the predictions were used
PP3 SupportingComputational evidence supports a splice-altering effect. SpliceAI predicts a strong splice impact with a maximum delta score of 0.99, which is above the ENIGMA PP3 threshold of 0.2 for predicted splicing impact. Details ▾Hide ▴
Rule
ENIGMA BRCA2 PP3_Supporting applies for predicted splicing impact when SpliceAI is ≥0.2.
Evidence considered
- SpliceAI max delta 0.99.
- REVEL 0.88.
- BayesDel 0.0862004.
Sources
BP4 Computational evidence does not support BP4. Although the BayesDel score is 0.086 and below the BRCA2 no-impact threshold of 0.18, SpliceAI is 0.99, which is above the BP4 requirement for no predicted splice impact at 0.1 or lower. Details ▾Hide ▴
Rule
ENIGMA BRCA2 BP4 requires no predicted protein or splicing impact, including SpliceAI ≤0.1.
Evidence considered
- BayesDel 0.0862004.
- SpliceAI max delta 0.99.
Sources
BP7 This is a missense variant with predicted splice impact rather than a synonymous or eligible intronic change with no splice effect, so BP7 is not met. Details ▾Hide ▴
Rule
ENIGMA BRCA2 BP7 is reserved for eligible synonymous or intronic variants, or RNA data showing no damaging splicing effect in the appropriate context.
Evidence considered
- Missense variant.
- SpliceAI max delta 0.99.
Sources
Statement
In silico
SpliceAI predicts possible splice impact for this variant (max delta score = 0.99). REVEL score = 0.88. BayesDel score = 0.0862004.
9 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata. None of the listed paper records explicitly indicates that the variant is named.
Recorded publications
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PMID 18424508 ↗Screening BRCA1 and BRCA2 unclassified variants for splicing mutations using reverse transcription PCR on patient RNA and an ex vivo assay based on a splicing reporter minigene.Bonnet C et al. · 2008No paper-specific finding is recorded.
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PMID 15290653 ↗Integrated evaluation of DNA sequence variants of unknown clinical significance: application to BRCA1 and BRCA2.Goldgar DE et al. · 2004No paper-specific finding is recorded.
-
PMID 15695382 ↗Functional evaluation and cancer risk assessment of BRCA2 unclassified variants.Wu K et al. · 2005No paper-specific finding is recorded.
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PMID 16489001 ↗Genetic and histopathologic evaluation of BRCA1 and BRCA2 DNA sequence variants of unknown clinical significance.Chenevix-Trench G et al. · 2006No paper-specific finding is recorded.
-
PMID 18607349 ↗Mouse embryonic stem cell-based functional assay to evaluate mutations in BRCA2.Kuznetsov SG et al. · 2008No paper-specific finding is recorded.
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PMID 22505045 ↗Guidelines for splicing analysis in molecular diagnosis derived from a set of 327 combined in silico/in vitro studies on BRCA1 and BRCA2 variants.Houdayer C et al. · 2012No paper-specific finding is recorded.
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PMID 23108138 ↗A classification model for BRCA2 DNA binding domain missense variants based on homology-directed repair activity.Guidugli L et al. · 2013No paper-specific finding is recorded.
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PMID 28492532 ↗Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.No paper-specific finding is recorded.
-
PMID 29192238 ↗Evaluation of reported pathogenic variants and their frequencies in a Japanese population based on a whole-genome reference panel of 2049 individuals.No paper-specific finding is recorded.
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
1 / 1,614,050 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.990
Open source ↗
ClinVar
14 Pathogenic · 3 Likely pathogenic
Open source ↗
COSMIC
Captured COSMIC source record
Open source ↗
Cancer hotspots
Captured Cancer Hotspots source record
Open source ↗
OncoKB
Captured OncoKB source record
Open source ↗
ClinGen CSpec
Captured ClinGen CSpec source record
Open source ↗
All source links
- ClinGen CSpec ↗cspec.genome.network/cspec/ui/svi/doc/1535438831
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/52475/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/13-32937362-A-G?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr13-32363225-A-G?dataset=gn…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000059.3%3Ac.8023…
- OncoKB ↗www.oncokb.org/gene/BRCA2/I2675V
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=BRCA2+c.8023A%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= 6.19559e-07; MAF= 0.00006%, 1/1614050 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 2.22836e-05; MAF= 0.00223%, 1/44876 alleles, homozygotes = 0).
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 3.98286e-06; MAF= 0.00040%, 1/251076 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 5.43833e-05; MAF= 0.00544%, 1/18388 alleles, homozygotes = 0).
ClinVar
This variant has been reported in ClinVar as Pathogenic (14 clinical laboratories) and as Likely pathogenic (3 clinical laboratories) and as Pathogenic by ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel, ClinGen (expert panel). (ClinVarID = 52475)
In silico
SpliceAI predicts possible splice impact for this variant (max delta score = 0.99). REVEL score = 0.88. BayesDel score = 0.0862004.
Functional
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Loss-of-function; curated oncogenicity label: Likely Oncogenic.
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.