0%
BRCA1c.5522G>AUncertain significance
Print report
Variant interpretation report

BRCA1 c.5522G>A, p.(Ser1841Asn)

NM_007294.3:c.5522G>A NP_009225.1:p.(Ser1841Asn) View identifiers
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.

About BRCA1

No gene-level summary was recorded for this case.

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: 1
Pathogenic criteria applied · 0

No pathogenic criterion marked as applied in the recorded assessment.

Benign criteria applied · 1
BP4Supporting
BP4 · supporting

This missense variant is located in the BRCA1 BRCT repeats, and the BRCA1 ENIGMA BP4 rule is met because BayesDel no-AF is 0.144191, which is at or below the benign threshold of 0.15, and SpliceAI predicts no significant splice effect with a maximum delta score of 0.00, which is at or below the threshold of 0.1. REVEL is 0.626, but the gene-specific BRCA1 VCEP computational rule is based on BayesDel and SpliceAI rather than REVEL.

Recorded classification: Uncertain significance

Official ENIGMA BRCA1 and BRCA2 Specification v1.2 Table 3 final-classification combination rules (CSPEC/VCEP framework).

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 / 1,614,094 alleles

gnomAD v4.1: 1 / 1,614,094 alleles. Recorded AF 6.19543e-07. Recorded homozygote count 0.

gnomAD v2.1

Absent from gnomAD v2.1.

No listed criterion applied
gnomAD v4.1 ↗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.

Applied · BP4 →
ClinVar submissions
Not recorded

A ClinVar laboratory submission summary was not recorded.

Context only ClinVar ↗
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
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
COSMIC ↗Cancer Hotspots ↗
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: 1 met · 8 not met · 8 not assessed · 11 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Pathogenic
PVS1PS1PS2PS3PS4PM1PM2PM3PM4PM5PM6PP1PP2PP3PP4PP5
Benign
BA1BS1BS2BS3BS4BP1BP2BP3BP4BP5BP6BP7
Met Not met Not assessed Not applicable

The BRCA1 c.5522G>A (p.Ser1841Asn; p.S1841N) variant has been reported in ClinVar with conflicting interpretations, including an expert-panel classification of uncertain significance.

This variant is absent from gnomAD v2.1 and present once in gnomAD v4.1 (1/1,614,094 alleles; AF 6.20e-07; highest South Asian AF 1.10e-05), so it is very rare but not absent from population databases.

In ENIGMA-calibrated functional studies, results were discordant, ranging from loss-of-function to intermediate effects, and ENIGMA Table 9 does not assign PS3 or BS3 for this variant.

This missense change lies in the BRCA1 BRCT repeats, and the BRCA1 ENIGMA computational rule supports BP4 because BayesDel no-AF is 0.144191 (threshold <=0.15) and SpliceAI maximum delta is 0.00 (threshold <=0.1); REVEL is 0.626 but is not the deciding rule in this VCEP framework.

Met · 1

BP4 SupportingThis missense variant is located in the BRCA1 BRCT repeats, and the BRCA1 ENIGMA BP4 rule is met because BayesDel no-AF is 0.144191, which is at or below the benign threshold of 0.15, and SpliceAI predicts no significant splice effect with a maximum delta score of 0.00, which is at or below the threshold of 0.1. REVEL is 0.626, but the gene-specific BRCA1 VCEP computational rule is based on BayesDel and SpliceAI rather than REVEL. Details ▾Hide ▴
Rule
BRCA1 ENIGMA BP4 applies to missense variants inside important domains when BayesDel no-AF <= 0.15 and SpliceAI <= 0.1.
Evidence considered
  • Protein location within BRCT repeats
  • BayesDel no-AF 0.144191 <= 0.15
  • SpliceAI max delta 0.00 <= 0.1
  • REVEL 0.626
Sources
vcep_specifications_v1_2_2024_11_18vcep_appendices_v1_2_2024_11_18bayesdelspliceai ↗revel

Not met · 8 · evaluated, threshold not reached

PVS1 This variant is a missense substitution, p.(Ser1841Asn) / p.(S1841N), and does not fall into the BRCA1 loss-of-function variant categories used for PVS1. SpliceAI predicts no significant splice impact with a maximum delta score of 0.00, so available evidence does not support a PVS1-based loss-of-function mechanism for this variant. Details ▾Hide ▴
Rule
BRCA1 ENIGMA PVS1 is for qualifying loss-of-function variants or qualifying RNA evidence; these conditions are not met here.
Evidence considered
  • Missense variant rather than a null variant
  • SpliceAI max delta score 0.00
Still missing
  • Variant-level RNA assay data would be needed to reconsider PVS1 on an RNA basis if abnormal splicing were suspected.
Sources
pvs1_variant_assessmentpvs1_gene_contextspliceai ↗vcep_specifications_v1_2_2024_11_18
PS3 ENIGMA-calibrated functional evidence for this variant is discordant across multiple studies, with reported results ranging from loss-of-function to intermediate effects. Because the available calibrated studies do not show a consistent damaging effect, PS3 is not met. Details ▾Hide ▴
Rule
BRCA1 ENIGMA PS3 requires well-established functional studies showing a consistent damaging effect; ENIGMA Table 9 does not assign PS3 for this variant.
Evidence considered
  • ENIGMA Table 9 assigns no PS3/BS3 code for c.5522G>A
  • Supplementary functional dataset lists functional impact as complete/partial with conflicting calibrated study outputs
Still missing
  • Additional calibrated functional evidence with consistent damaging results would be needed to support PS3.
Sources
vcep_specifications_table9_v1_2_2024_11_18vcep_supplementarytables_v1_2_2024_11_18
PM2 This variant is absent from gnomAD v2.1 but is present in gnomAD v4.1 at 1/1,614,094 alleles (AF 6.20e-07; highest population AF 1.10e-05 in South Asian individuals). Because the variant is not absent from population databases, PM2 is not met. Details ▾Hide ▴
Rule
BRCA1 ENIGMA PM2 requires absence from controls in the specified gnomAD datasets.
Evidence considered
  • gnomAD v2.1 absent
  • gnomAD v4.1 present once
  • no homozygotes
Still missing
  • A qualifying absence-based population assessment would require absence in the relevant control datasets used by the BRCA1 ENIGMA rule.
Sources
gnomad_v2 ↗gnomad_v4 ↗vcep_specifications_v1_2_2024_11_18
PP3 This missense variant is located in the BRCA1 BRCT repeats, but the BRCA1 ENIGMA PP3 rule is not met because BayesDel no-AF is 0.144191, which is below the pathogenic threshold of 0.28, and SpliceAI predicts no splice effect with a maximum delta score of 0.00, below the splicing threshold of 0.2. REVEL is 0.626, but the gene-specific VCEP computational rule is based on BayesDel and SpliceAI rather than REVEL. Details ▾Hide ▴
Rule
BRCA1 ENIGMA PP3 for missense variants in important domains requires BayesDel no-AF >= 0.28, or qualifying splice prediction with SpliceAI >= 0.2.
Evidence considered
  • Protein location within BRCT repeats
  • BayesDel no-AF 0.144191
  • SpliceAI max delta 0.00
  • REVEL 0.626
Sources
vcep_specifications_v1_2_2024_11_18vcep_appendices_v1_2_2024_11_18bayesdelspliceai ↗revel
BA1 This variant does not meet the BRCA1 ENIGMA BA1 threshold. It is absent from gnomAD v2.1 and present in gnomAD v4.1 at AF 6.20e-07, which is far below the BA1 stand-alone threshold of 0.001. Details ▾Hide ▴
Rule
BRCA1 ENIGMA BA1 requires filter allele frequency > 0.001.
Evidence considered
  • gnomAD v4.1 total AF 6.195426040862552e-07
Sources
gnomad_v2 ↗gnomad_v4 ↗vcep_specifications_v1_2_2024_11_18
BS1 This variant does not meet the BRCA1 ENIGMA BS1 threshold. The observed gnomAD v4.1 allele frequency is 6.20e-07, which is below both the supporting threshold of 0.00002 and the strong threshold of 0.0001. Details ▾Hide ▴
Rule
BRCA1 ENIGMA BS1 requires filter allele frequency > 0.00002 for supporting or > 0.0001 for strong evidence.
Evidence considered
  • gnomAD v4.1 total AF 6.195426040862552e-07
Sources
gnomad_v4 ↗vcep_specifications_v1_2_2024_11_18
BS3 ENIGMA-calibrated functional studies for this variant are discordant and do not consistently show a normal or non-damaging effect. Because ENIGMA Table 9 does not assign BS3 for this variant, BS3 is not met. Details ▾Hide ▴
Rule
BRCA1 ENIGMA BS3 requires well-established studies showing no damaging effect; ENIGMA Table 9 does not assign BS3 for this variant.
Evidence considered
  • ENIGMA Table 9 assigns no BS3 code for c.5522G>A
  • Supplementary functional dataset shows conflicting calibrated results
Still missing
  • Additional calibrated functional evidence showing a consistent non-damaging effect would be needed to support BS3.
Sources
vcep_specifications_table9_v1_2_2024_11_18vcep_supplementarytables_v1_2_2024_11_18
BP1 This missense variant is located in the BRCA1 BRCT repeats, a clinically important functional domain spanning amino acids 1650-1857, so it does not meet the BRCA1 ENIGMA BP1 rule for missense variants outside important domains. SpliceAI also predicts no splice effect, but the domain requirement is not met. Details ▾Hide ▴
Rule
BRCA1 ENIGMA BP1_Strong applies to missense variants outside important domains with no predicted splice effect.
Evidence considered
  • Protein position Ser1841 within BRCT repeats
  • SpliceAI max delta 0.00
Sources
vcep_specifications_v1_2_2024_11_18vcep_appendices_v1_2_2024_11_18spliceai ↗

Not assessed · 8 · no assessment recorded

PS1 No evidence was identified showing that this variant produces the same established pathogenic protein or splicing consequence as another previously classified BRCA1 variant, so PS1 was not assessed. Details ▾Hide ▴
Rule
BRCA1 ENIGMA PS1 requires the same pathogenic protein or splicing consequence as a previously classified variant.
Evidence considered
  • Missense variant with no predicted splice effect by SpliceAI
Still missing
  • A validated BRCA1-specific same-amino-acid or same-splicing comparison would be needed for PS1.
Sources
vcep_specifications_v1_2_2024_11_18spliceai ↗
PS4 No case-control analysis or formal evidence showing that this variant is significantly enriched in affected individuals compared with controls was identified, so PS4 was not assessed. Details ▾Hide ▴
Rule
BRCA1 ENIGMA PS4 requires significant enrichment in affected individuals versus controls.
Evidence considered
  • ClinVar reports conflicting clinical interpretations but no qualifying case-control statistic
Still missing
  • A variant-specific case-control dataset with odds ratio and confidence interval would be needed for PS4.
Sources
clinvar ↗vcep_specifications_v1_2_2024_11_18
PM3 No evidence was identified that this variant was observed with an appropriate BRCA1-related Fanconi anemia phenotype and a qualifying second BRCA1 variant in trans, so PM3 was not assessed. Details ▾Hide ▴
Rule
BRCA1 ENIGMA PM3 is limited to specific recessive Fanconi anemia contexts.
Evidence considered
  • No qualifying recessive-disease case data identified
Still missing
  • Phenotype and phase data would be needed for PM3.
Sources
vcep_specifications_v1_2_2024_11_18
PP1 No quantitative co-segregation data were identified for this variant, so PP1 was not assessed. Details ▾Hide ▴
Rule
BRCA1 ENIGMA PP1 requires quantitative co-segregation evidence.
Evidence considered
  • No qualifying segregation dataset identified
Still missing
  • Informative family segregation data with a quantitative likelihood ratio would be needed for PP1.
Sources
vcep_specifications_v1_2_2024_11_18
PP4 No variant-specific multifactorial clinical-history likelihood ratio meeting the BRCA1 ENIGMA PP4 thresholds was identified for this variant, so PP4 was not assessed. Details ▾Hide ▴
Rule
BRCA1 ENIGMA PP4 requires a qualifying multifactorial clinical likelihood ratio toward pathogenicity.
Evidence considered
  • No exact qualifying PP4 likelihood-ratio entry identified for c.5522G>A in the BRCA1 clinical-history LR table
Still missing
  • An exact variant-level clinical-history likelihood ratio of at least 2.08 would be needed for PP4.
Sources
vcep_pmid_31853058_brca1_clinical_history_lrPMID:31853058 ↗vcep_specifications_v1_2_2024_11_18
BS2 No qualifying data were identified showing this variant in individuals without features of BRCA1-related Fanconi anemia under the BRCA1 ENIGMA point-based BS2 framework, so BS2 was not assessed. Details ▾Hide ▴
Rule
BRCA1 ENIGMA BS2 requires qualifying observations scored under the recessive-disease framework.
Evidence considered
  • No BS2 point-based dataset identified
Still missing
  • Qualifying phenotype and observation data would be needed for BS2.
Sources
vcep_specifications_v1_2_2024_11_18
BS4 No quantitative non-segregation data were identified for this variant, so BS4 was not assessed. Details ▾Hide ▴
Rule
BRCA1 ENIGMA BS4 requires quantitative evidence of lack of segregation.
Evidence considered
  • No qualifying non-segregation dataset identified
Still missing
  • Informative family data with a likelihood ratio against pathogenicity would be needed for BS4.
Sources
vcep_specifications_v1_2_2024_11_18
BP5 No variant-specific multifactorial clinical-history likelihood ratio meeting the BRCA1 ENIGMA BP5 thresholds was identified for this variant, so BP5 was not assessed. Details ▾Hide ▴
Rule
BRCA1 ENIGMA BP5 requires a qualifying multifactorial clinical likelihood ratio against pathogenicity.
Evidence considered
  • No exact qualifying BP5 likelihood-ratio entry identified for c.5522G>A in the BRCA1 clinical-history LR table
Still missing
  • An exact variant-level clinical-history likelihood ratio of 0.48 or lower would be needed for BP5.
Sources
vcep_pmid_31853058_brca1_clinical_history_lrPMID:31853058 ↗vcep_specifications_v1_2_2024_11_18
Not applicable · 11· recorded as not applicable Show reasons ▾Hide reasons ▴
PS2 N/ADe novo evidence is not used for BRCA1 in this VCEP framework, so PS2 is not applicable. Details ▾Hide ▴
Rule
Not applicable in the BRCA1 ENIGMA specification.
Evidence considered
  • BRCA1 ENIGMA specification marks PS2 as not applicable
Sources
vcep_specifications_v1_2_2024_11_18
PM1 N/APM1 is not applicable in the BRCA1 ENIGMA specification. Details ▾Hide ▴
Rule
Not applicable in the BRCA1 ENIGMA specification.
Evidence considered
  • BRCA1 ENIGMA specification marks PM1 as not applicable
Sources
vcep_specifications_v1_2_2024_11_18
PM4 N/APM4 is not applicable in the BRCA1 ENIGMA specification. Details ▾Hide ▴
Rule
Not applicable in the BRCA1 ENIGMA specification.
Evidence considered
  • BRCA1 ENIGMA specification marks PM4 as not applicable
Sources
vcep_specifications_v1_2_2024_11_18
PM5 N/AUnder the BRCA1 ENIGMA specification, PM5 is used here for protein-truncating variants in eligible exons. This variant is a missense substitution, so PM5 is not applicable. Details ▾Hide ▴
Rule
BRCA1 ENIGMA PM5 in this framework is the PM5_PTC rule for eligible truncating variants.
Evidence considered
  • Variant type is missense
  • not protein-truncating
Sources
vcep_specifications_v1_2_2024_11_18vcep_specifications_table4_v1_2_2024_11_18
PM6 N/APM6 is not applicable in the BRCA1 ENIGMA specification. Details ▾Hide ▴
Rule
Not applicable in the BRCA1 ENIGMA specification.
Evidence considered
  • BRCA1 ENIGMA specification marks PM6 as not applicable
Sources
vcep_specifications_v1_2_2024_11_18
PP2 N/APP2 is not applicable in the BRCA1 ENIGMA specification. Details ▾Hide ▴
Rule
Not applicable in the BRCA1 ENIGMA specification.
Evidence considered
  • BRCA1 ENIGMA specification marks PP2 as not applicable
Sources
vcep_specifications_v1_2_2024_11_18
PP5 N/APP5 is not applicable in the BRCA1 ENIGMA specification. Details ▾Hide ▴
Rule
Not applicable in the BRCA1 ENIGMA specification.
Evidence considered
  • BRCA1 ENIGMA specification marks PP5 as not applicable
Sources
vcep_specifications_v1_2_2024_11_18
BP2 N/ABP2 is not applicable in the BRCA1 ENIGMA specification. Details ▾Hide ▴
Rule
Not applicable in the BRCA1 ENIGMA specification.
Evidence considered
  • BRCA1 ENIGMA specification marks BP2 as not applicable
Sources
vcep_specifications_v1_2_2024_11_18
BP3 N/ABP3 is not applicable in the BRCA1 ENIGMA specification. Details ▾Hide ▴
Rule
Not applicable in the BRCA1 ENIGMA specification.
Evidence considered
  • BRCA1 ENIGMA specification marks BP3 as not applicable
Sources
vcep_specifications_v1_2_2024_11_18
BP6 N/ABP6 is not applicable in the BRCA1 ENIGMA specification. Details ▾Hide ▴
Rule
Not applicable in the BRCA1 ENIGMA specification.
Evidence considered
  • BRCA1 ENIGMA specification marks BP6 as not applicable
Sources
vcep_specifications_v1_2_2024_11_18
BP7 N/AThis variant is a missense substitution within a clinically important BRCT domain, and no qualifying RNA-only evidence showing a benign transcript effect was identified. The BRCA1 ENIGMA BP7 rules do not apply to this variant in its current evidence context. Details ▾Hide ▴
Rule
BRCA1 ENIGMA BP7 is primarily for silent or intronic variants, or for specific RNA-only benign evidence scenarios.
Evidence considered
  • Missense variant in BRCT domain
  • SpliceAI max delta 0.00
  • No qualifying benign RNA assay evidence identified
Still missing
  • Variant-level RNA data showing a benign transcript effect would be needed before reconsidering BP7-related RNA evidence.
Sources
vcep_specifications_v1_2_2024_11_18spliceai ↗

Identifiers

Gene
BRCA1
Transcript
NM_007294.3
Coding (HGVS c.)
NM_007294.3:c.5522G>A
Protein (HGVS p.)
NP_009225.1:p.(Ser1841Asn)
GRCh38
chr17:43045748 C>T
GRCh37
chr17:41197765 C>T

Gene diagram

Every interpreted variant in BRCA1, mapped onto the exon structure of NM_007294.3. Select a row to find it on the plot.

BRCA1NM_007294.3
Fetching transcript structure from UCSC…
gnomAD v4.1 1 / 1,614,094 alleles AF 6.2e-07 · 0 homozygotes
gnomAD v2.1 Allele count data not recorded

By genetic ancestry

gnomAD v4.1

AF 6.2e-07 · 1 / 1,614,094 alleles · 0 hom
South Asian1 / 91,076 1.1e-05
0 alternate alleles recorded in 9 other groups: Remaining individuals, Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, Ashkenazi Jewish, African/African American, European (non-Finnish).

Statements

gnomAD v4.1

This variant is present in gnomAD v4.1 (AF= 6.19543e-07; MAF= 0.00006%, 1/1614094 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 1.09798e-05; MAF= 0.00110%, 1/91076 alleles, homozygotes = 0).

gnomAD v2.1

Absent from gnomAD v2.1.

Other predictors

REVEL
Not available
BayesDel
Not available

How the predictions were used

BP4 SupportingThis missense variant is located in the BRCA1 BRCT repeats, and the BRCA1 ENIGMA BP4 rule is met because BayesDel no-AF is 0.144191, which is at or below the benign threshold of 0.15, and SpliceAI predicts no significant splice effect with a maximum delta score of 0.00, which is at or below the threshold of 0.1. REVEL is 0.626, but the gene-specific BRCA1 VCEP computational rule is based on BayesDel and SpliceAI rather than REVEL. Details ▾Hide ▴
Rule
BRCA1 ENIGMA BP4 applies to missense variants inside important domains when BayesDel no-AF <= 0.15 and SpliceAI <= 0.1.
Evidence considered
  • Protein location within BRCT repeats
  • BayesDel no-AF 0.144191 <= 0.15
  • SpliceAI max delta 0.00 <= 0.1
  • REVEL 0.626
Sources
vcep_specifications_v1_2_2024_11_18vcep_appendices_v1_2_2024_11_18bayesdelspliceai ↗revel
PP3 This missense variant is located in the BRCA1 BRCT repeats, but the BRCA1 ENIGMA PP3 rule is not met because BayesDel no-AF is 0.144191, which is below the pathogenic threshold of 0.28, and SpliceAI predicts no splice effect with a maximum delta score of 0.00, below the splicing threshold of 0.2. REVEL is 0.626, but the gene-specific VCEP computational rule is based on BayesDel and SpliceAI rather than REVEL. Details ▾Hide ▴
Rule
BRCA1 ENIGMA PP3 for missense variants in important domains requires BayesDel no-AF >= 0.28, or qualifying splice prediction with SpliceAI >= 0.2.
Evidence considered
  • Protein location within BRCT repeats
  • BayesDel no-AF 0.144191
  • SpliceAI max delta 0.00
  • REVEL 0.626
Sources
vcep_specifications_v1_2_2024_11_18vcep_appendices_v1_2_2024_11_18bayesdelspliceai ↗revel
BP7 N/AThis variant is a missense substitution within a clinically important BRCT domain, and no qualifying RNA-only evidence showing a benign transcript effect was identified. The BRCA1 ENIGMA BP7 rules do not apply to this variant in its current evidence context. Details ▾Hide ▴
Rule
BRCA1 ENIGMA BP7 is primarily for silent or intronic variants, or for specific RNA-only benign evidence scenarios.
Evidence considered
  • Missense variant in BRCT domain
  • SpliceAI max delta 0.00
  • No qualifying benign RNA assay evidence identified
Still missing
  • Variant-level RNA data showing a benign transcript effect would be needed before reconsidering BP7-related RNA evidence.
Sources
vcep_specifications_v1_2_2024_11_18spliceai ↗

Statement

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.626. BayesDel score = 0.144191.

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 1 / 1,614,094 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

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= 6.19543e-07; MAF= 0.00006%, 1/1614094 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 1.09798e-05; MAF= 0.00110%, 1/91076 alleles, homozygotes = 0).

gnomAD v2.1

Absent from gnomAD v2.1.

ClinVar

This variant has been reported in ClinVar as Likely pathogenic (4 clinical laboratories) and as Uncertain significance (1 clinical laboratory) and as Pathogenic (1 clinical laboratory) and as likely pathogenic (1 clinical laboratory) and as Uncertain Significance 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). REVEL score = 0.626. BayesDel score = 0.144191.

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.