About BARD1
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
BARD1 c.221G>T, p.(Cys74Phe)
Classification
Uncertain significance
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is uncertain. Select a step to read what it means.
Uncertain.The recorded classification is uncertain significance.
In plain language
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.
LYFE Sciences is an AI system, and it can make mistakes.
Criteria may be applied incorrectly, sources may be misread, and a
confident-looking classification can still be wrong.
Double-check every criterion and its underlying evidence
before relying on any call.
01The reasoning
How it was classified
The recorded framework is Not recorded. 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: 3
Benign evidence criteria: 0
Pathogenic criteria applied · 3
PM1Moderate
PM1 · moderate
The variant c.221G>T produces p.Cys74Phe, which resides in the BARD1 RING finger domain (residues ~46-90). The RING domain is critical for BARD1-BRCA1 heterodimerization and E3 ubiquitin ligase activity. C74 is a conserved cysteine within the zinc-coordinating RING structure. Missense alteration of a structurally critical RING domain residue meets PM1 at moderate strength per generic ACMG/AMP criteria.
PM2Moderate
PM2 · moderate
NM_000465.4:c.221G>T is absent from gnomAD v2.1 and present at very low frequency in gnomAD v4.1 (overall AF = 9.19e-05, 0.0092%; grpmax FAF = 8.91e-05). The allele frequency is well below the 0.1% threshold for PM2 application. Highest subpopulation frequency is in Ashkenazi Jewish (AF = 0.000112, 0.011%). No homozygotes observed.
PP3Supporting
PP3 · supporting
Multiple in silico predictors support a deleterious effect for NM_000465.4:c.221G>T (p.Cys74Phe). REVEL score is 0.932, which is strongly predictive of pathogenicity (well above the 0.7 threshold). BayesDel score is 0.560, indicating moderate deleterious potential. SpliceAI predicts no significant splicing impact (max delta = 0.05), which does not contradict the missense assessment.
Benign criteria applied · 0
No benign criterion marked as applied in the recorded assessment.
Recorded classification: Uncertain significance
gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: PM1 moderate, PM2 moderate, PP3 supporting; combination = 2 moderate + 1 supporting, which maps to VUS.
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
135 / 1,469,506 alleles
gnomAD v4.1: 135 / 1,469,506 alleles. Recorded AF 9.18676e-05. Recorded homozygote count 0.
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI score
0.050 maximum delta
Recorded SpliceAI maximum delta score: 0.050. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
6 reported laboratory submissions
6 Uncertain significance. ClinVar API review status: criteria provided, multiple submitters, no conflicts.
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. BARD1, a tumor suppressor involved in the DNA damage response, is altered by mutation in breast and ovarian cancers.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
3 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV107297670, n = 3 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under Not recorded, with the data and sources behind each one.
26 criteria with recorded statuses: 3 met · 21 not met · 0 not assessed · 2 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
This variant resides in the BARD1 RING finger domain (p.Cys74Phe), a critical functional domain required for BRCA1 heterodimerization and E3 ubiquitin ligase activity.
The variant is extremely rare in population databases: absent from gnomAD v2.1 and observed at 0.0092% (135/1,469,506 alleles, 0 homozygotes) in gnomAD v4.1, meeting PM2 threshold (<0.1%).
Multiple in silico predictors support a deleterious effect: REVEL score 0.932 (strongly damaging), BayesDel score 0.560 (moderately deleterious). No splicing impact is predicted (SpliceAI max delta 0.05).
No functional studies have been reported for this variant. OncoKB reports unknown oncogenic effect. Six clinical laboratories in ClinVar classify this variant as Uncertain significance with 1-star review status.
No de novo observations, segregation data, case-control enrichment, or same-residue pathogenic comparators were identified. No literature publication mentions this specific variant.
Applying generic ACMG/AMP 2015 criteria: PM1 (RING domain) + PM2 (rare in population) + PP3 (in silico damaging) = 2 moderate + 1 supporting pathogenic criteria, with zero benign criteria met. This combination is insufficient for Likely Pathogenic classification and supports a classification of Uncertain significance.
No criteria match.
Met · 3
PM1 ModerateThe variant c.221G>T produces p.Cys74Phe, which resides in the BARD1 RING finger domain (residues ~46-90). The RING domain is critical for BARD1-BRCA1 heterodimerization and E3 ubiquitin ligase activity. C74 is a conserved cysteine within the zinc-coordinating RING structure. Missense alteration of a structurally critical RING domain residue meets PM1 at moderate strength per generic ACMG/AMP criteria. Details ▾Hide ▴
Evidence considered
- p.Cys74Phe maps to the BARD1 RING finger domain (residues ~46-90)
- RING domain is critical for BARD1-BRCA1 heterodimerization and ubiquitin ligase function
- C74 is a structurally conserved cysteine in the zinc-coordinating RING architecture
Sources
PM2 ModerateNM_000465.4:c.221G>T is absent from gnomAD v2.1 and present at very low frequency in gnomAD v4.1 (overall AF = 9.19e-05, 0.0092%; grpmax FAF = 8.91e-05). The allele frequency is well below the 0.1% threshold for PM2 application. Highest subpopulation frequency is in Ashkenazi Jewish (AF = 0.000112, 0.011%). No homozygotes observed. Details ▾Hide ▴
Evidence considered
- Absent from gnomAD v2.1 (exomes)
- gnomAD v4.1: 135/1
- 469
- 506 alleles (AF = 9.19e-05
- 0.0092%)
- 0 homozygotes
- grpmax FAF = 8.91e-05
- below 0.1% PM2 threshold
- Absent from gnomAD-Canada v1.0
Sources
PP3 SupportingMultiple in silico predictors support a deleterious effect for NM_000465.4:c.221G>T (p.Cys74Phe). REVEL score is 0.932, which is strongly predictive of pathogenicity (well above the 0.7 threshold). BayesDel score is 0.560, indicating moderate deleterious potential. SpliceAI predicts no significant splicing impact (max delta = 0.05), which does not contradict the missense assessment. Details ▾Hide ▴
Evidence considered
- REVEL: 0.932 (deleterious
- above 0.7 threshold)
- BayesDel: 0.560 (moderate deleterious prediction)
- SpliceAI: max delta 0.05 (no splice impact
- not contradictory)
Sources
Not met · 21 · evaluated, threshold not reached
PS1 PS1 requires the same amino acid change (p.Cys74Phe) from a different nucleotide change to be previously established as pathogenic. No evidence was identified of a different nucleotide substitution producing p.Cys74Phe with an established pathogenic classification. Details ▾Hide ▴
Evidence considered
- No alternative nucleotide change yielding p.Cys74Phe identified in ClinVar or literature
Still missing
- No alternative nucleotide variant producing C74F was found
Sources
PS2 PS2 requires confirmed de novo occurrence. No de novo data were identified for NM_000465.4:c.221G>T in any available source. Details ▾Hide ▴
Evidence considered
- No de novo reports found in ClinVar submissions or literature
Still missing
- No de novo testing data available
PS3 PS3 requires well-established functional studies demonstrating a deleterious effect. No variant-specific or range-characterizing functional studies were identified for NM_000465.4:c.221G>T (p.Cys74Phe). The Color Health ClinVar submission (SCV000905903) explicitly noted that functional studies have not been reported for this variant. OncoKB reports Unknown Oncogenic Effect with no variant-specific reviewed functional evidence. Details ▾Hide ▴
Evidence considered
- Color Health submission: 'to our knowledge
- functional studies have not been reported for this variant'
- OncoKB: Unknown Oncogenic Effect
- no variant-specific functional evidence
- No publications with functional data for this variant
Still missing
- No functional studies exist for this variant
Sources
PS4 PS4 requires a significantly increased prevalence of the variant in affected individuals compared to controls. No case-control data or statistical enrichment analysis was identified. The literature papers indexed under PS4 (24366376, 24366402, 24432435, 25394175, 26389258) are generic clinical practice guidelines and do not report variant-specific case observations. Details ▾Hide ▴
Evidence considered
- No case-control data or enriched prevalence in affected individuals available
Still missing
- No case-control or cohort enrichment data
PM5 PM5 requires a different missense change at the same amino acid residue (p.Cys74) to be classified as pathogenic. Automated candidate harvesting found no same-residue pathogenic or likely pathogenic comparators for this position. Manual review of available evidence also did not identify any pathogenic comparator at residue 74. Details ▾Hide ▴
Evidence considered
- PM5 candidate search: 0 same-residue candidates found
- No pathogenic/likely pathogenic variant at p.Cys74 other than C74F
Still missing
- No pathogenic comparator at same residue position
Sources
pm5_candidates
PM6 PM6 requires a de novo observation without confirmation of paternity and maternity. No de novo data are available for this variant. Details ▾Hide ▴
Evidence considered
- No de novo reports identified
Still missing
- No de novo testing data
PP1 PP1 requires cosegregation of the variant with disease in multiple affected family members. No segregation data are available for this variant. Details ▾Hide ▴
Evidence considered
- No segregation or family study data available
Still missing
- No segregation data
PP2 PP2 requires a low rate of benign missense variation in the gene and missense variants as a common disease mechanism. BARD1 is primarily a loss-of-function tumor suppressor; the gene's Z-score for missense constraint and rate of benign missense variation do not clearly meet PP2 criteria. Additionally, HCI prior data was not available for BARD1 in this analysis. Details ▾Hide ▴
Evidence considered
- BARD1: tumor suppressor
- primarily LoF mechanism
- HCI prior not available for BARD1
- Insufficient evidence for low benign missense rate
Still missing
- No HCI prior or gene-level missense constraint metrics available
PP4 PP4 requires the patient's phenotype or family history to be highly specific for the disease associated with the gene. No patient-specific phenotype or family history data are available for assessment. Details ▾Hide ▴
Evidence considered
- No patient phenotype or family history data available
Still missing
- No patient phenotype data provided
PP5 PP5 requires a reputable source to have reported the variant as pathogenic. In ClinVar, this variant (Variation ID: 234046) is classified as Uncertain significance by 6 clinical laboratories with review status 'criteria provided, single submitter' (1-star). No expert panel (3-star) classification exists. The ClinVar status does not meet the threshold for PP5 application. Literature indexed under PP5 (24366376, 24366402, 24432435, 25394175, 26389258) are generic clinical guideline documents that do not mention this specific variant. Details ▾Hide ▴
Evidence considered
- ClinVar: Uncertain significance (6 submitters
- 1-star review status)
- No expert panel review or 3-star classification
- No literature reports this variant as pathogenic
Still missing
- No authoritative source classifies this variant as pathogenic
Sources
BA1 BA1 requires allele frequency >1% in population databases. The highest observed frequency is in gnomAD v4.1 Ashkenazi Jewish population (AF = 0.011%), well below the 1% threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 overall AF = 0.0092%
- highest subpopulation (ASJ) AF = 0.011%
- Far below 1% BA1 threshold
Sources
BS1 BS1 requires allele frequency >0.3% in population databases. The highest observed frequency is 0.011%, well below the 0.3% threshold. Details ▾Hide ▴
BS2 BS2 requires observation in a healthy adult homozygous for a recessive disorder, or observation in trans with a pathogenic variant for a fully penetrant dominant disorder. No such data are available for this variant. Details ▾Hide ▴
Evidence considered
- No homozygous or in trans observations reported
Still missing
- No trans or homozygous data available
BS3 BS3 requires well-established functional studies demonstrating no deleterious effect. No functional studies (supporting or refuting) were identified for this variant. Details ▾Hide ▴
Evidence considered
- No functional studies available for this variant
Still missing
- No functional data exist
BS4 BS4 requires lack of segregation with disease in affected family members. No segregation data are available for this variant. Details ▾Hide ▴
Evidence considered
- No segregation data available
Still missing
- No segregation or family study data
BP1 BP1 applies to missense variants in genes where primarily truncating variants cause disease. While BARD1 is a tumor suppressor where loss-of-function is a recognized disease mechanism, missense variants within the RING domain (where p.Cys74Phe resides) have established pathogenic potential through disruption of BARD1-BRCA1 heterodimerization and E3 ubiquitin ligase activity. A RING domain missense is not appropriately downgraded by BP1, consistent with the evidence symmetry principle applied to PM1. Details ▾Hide ▴
Evidence considered
- BARD1: LoF is the primary disease mechanism
- RING domain missense variants have known pathogenic potential
- Evidence symmetry with PM1: RING domain criticality supports pathogenic role
BP2 BP2 requires observation in trans with a pathogenic variant for a fully penetrant dominant disorder. No such observations are available. Details ▾Hide ▴
Evidence considered
- No in trans observations reported
Still missing
- No trans configuration data
BP4 BP4 requires multiple lines of computational evidence suggesting no impact on gene product. REVEL score is 0.932, strongly predicting a deleterious effect, and BayesDel is 0.560 (moderately deleterious). These scores contradict BP4 application. Details ▾Hide ▴
Evidence considered
- REVEL: 0.932 (damaging prediction
- contradicts BP4)
- BayesDel: 0.560 (moderate deleterious prediction
Sources
revelbayesdel
BP5 BP5 requires the variant to be found in a case with an alternate molecular basis for disease. No such data are available. Details ▾Hide ▴
Evidence considered
- No alternate molecular basis data available
Still missing
- No data on alternate molecular diagnoses
BP6 BP6 requires a reputable source to have reported the variant as benign. ClinVar classifies this variant as Uncertain significance (6 submitters, 1-star review). No reputable source reports it as benign or likely benign. Details ▾Hide ▴
Evidence considered
- ClinVar: Uncertain significance
- not benign/likely benign
- No authoritative benign classification available
Sources
PS5 PS5 (not a standard ACMG/AMP 2015 criterion) would require very strong evidence level functional or clinical data. No variant-specific data meeting this threshold were identified. Details ▾Hide ▴
Evidence considered
- No evidence meeting very strong criterion threshold
Still missing
- PS5 is not a standard ACMG criterion
- no applicable evidence
Not applicable · 2· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/APVS1 is not applicable to missense variants. NM_000465.4:c.221G>T is a missense substitution (p.Cys74Phe) and does not fall into any null-variant category (nonsense, frameshift, or canonical ±1,2 splice consensus variants). The generic PVS1 framework per PMC6185798 does not apply to this variant class (variant_bucket: 'other', apply_generic_pvs1_framework: false). Details ▾Hide ▴
Evidence considered
- Missense variant (c.221G>T
- p.Cys74Phe) in exon 3
- Not a null variant: no nonsense
- frameshift
- or canonical splice disruption
- Generic PVS1 decision framework (PMC6185798) does not apply
Sources
pvs1_generic_framework ↗pvs1_variant_assessment
BP7 N/ABP7 applies to synonymous variants with no predicted splicing impact. NM_000465.4:c.221G>T is a missense variant (p.Cys74Phe), not synonymous. Details ▾Hide ▴
Evidence considered
- Missense substitution (G>T at c.221)
- not synonymous
Identifiers
- Gene
- BARD1
- Transcript
- NM_000465.4
- Coding (HGVS c.)
- NM_000465.4:c.221G>T
- Protein (HGVS p.)
- NP_000456.2:p.(Cys74Phe)
- GRCh38
- chr2:214792440 C>A
- GRCh37
- chr2:215657164 C>A
- ClinVar
- 234046
- COSMIC
- COSV107297670
Gene diagram
Every interpreted variant in BARD1, mapped onto the exon structure of NM_000465.4. Select a row to find it on the plot.
BARD1NM_000465.4
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 BARD1
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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
135 / 1,469,506 alleles
AF 9.19e-05 · 0 homozygotes · FAF 8.91e-05
gnomAD v2.1
Allele count data not recorded
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 9.2e-05 · 135 / 1,469,506 alleles · 0 hom · FAF 8.9e-05
| Ashkenazi Jewish3 / 26,718 | 0.00011 |
| European (Finnish)6 / 56,436 | 0.00011 |
| European (non-Finnish)114 / 1,082,550 | 0.00011 |
| African/African American5 / 66,582 | 7.5e-05 |
| Remaining individuals4 / 56,148 | 7.1e-05 |
| South Asian3 / 82,260 | 3.6e-05 |
0 alternate alleles recorded in 4 other groups: Admixed American, Amish, East Asian, Middle Eastern.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 9.18676e-05; MAF= 0.00919%, 135/1469506 alleles, homozygotes = 0) and has highest observed frequency in the Ashkenazi Jewish population (AF= 0.000112284; MAF= 0.01123%, 3/26718 alleles, homozygotes = 0); grpmax FAF= 8.91e-05.
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.932
- BayesDel
- 0.560
How the predictions were used
PP3 SupportingMultiple in silico predictors support a deleterious effect for NM_000465.4:c.221G>T (p.Cys74Phe). REVEL score is 0.932, which is strongly predictive of pathogenicity (well above the 0.7 threshold). BayesDel score is 0.560, indicating moderate deleterious potential. SpliceAI predicts no significant splicing impact (max delta = 0.05), which does not contradict the missense assessment. Details ▾Hide ▴
Evidence considered
- REVEL: 0.932 (deleterious
- above 0.7 threshold)
- BayesDel: 0.560 (moderate deleterious prediction)
- SpliceAI: max delta 0.05 (no splice impact
- not contradictory)
Sources
BP4 BP4 requires multiple lines of computational evidence suggesting no impact on gene product. REVEL score is 0.932, strongly predicting a deleterious effect, and BayesDel is 0.560 (moderately deleterious). These scores contradict BP4 application. Details ▾Hide ▴
Evidence considered
- REVEL: 0.932 (damaging prediction
- contradicts BP4)
- BayesDel: 0.560 (moderate deleterious prediction
Sources
revelbayesdel
BP7 N/ABP7 applies to synonymous variants with no predicted splicing impact. NM_000465.4:c.221G>T is a missense variant (p.Cys74Phe), not synonymous. Details ▾Hide ▴
Evidence considered
- Missense substitution (G>T at c.221)
- not synonymous
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.05). REVEL score = 0.932. BayesDel score = 0.560394.
7 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 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.Standards and guidelines for the interpretation of sequence variants (ACMG/AMP 2015). A methods paper describing the variant classification framework. NM_000465.4:c.221G>T was not identified in this paper; cited only as the canonical reference for the ACMG/AMP classification framework.Does not name this variant
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PMID 26467025 ↗A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.A standardized DNA variant scoring system for pathogenicity assessments in Mendelian disorders. Describes a rules-based scoring approach for variant classification. NM_000465.4:c.221G>T was not identified in this paper.Does not name this variant
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PMID 24366376 ↗Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women: U.S. Preventive Services Task Force recommendation statement.Moyer VA et al. · 2014USPSTF recommendation statement on risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women. Focuses exclusively on BRCA1 and BRCA2 testing; BARD1 and NM_000465.4:c.221G>T are not discussed.Does not name this variant
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PMID 24366402 ↗Summaries for patients. Assessing the genetic risk for BRCA-related breast or ovarian cancer in women: recommendations from the U.S. Preventive Services Task Force.2014Patient summary of the USPSTF recommendations for BRCA-related cancer genetic risk assessment. Discusses BRCA testing at a patient-education level. NM_000465.4:c.221G>T and BARD1 are not mentioned.Does not name this variant
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PMID 24432435 ↗PMID 24432435Nelson HD et al. · 2013No paper-specific finding is recorded.
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PMID 25394175 ↗A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment.Hampel H et al. · 2015ACMG/NSGC practice guideline on referral indications for cancer predisposition assessment. Provides general guidance on when to refer for cancer genetics evaluation. NM_000465.4:c.221G>T and BARD1 are not mentioned.Does not name this variant
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PMID 26389258 ↗Cancer Genetics Risk Assessment and Counseling (PDQ®): Health Professional Version.PDQ Cancer Genetics Editorial Board · 2002PDQ cancer genetics risk assessment and counseling summary (health professional version). A general reference document on cancer genetics counseling. NM_000465.4:c.221G>T and BARD1 are not mentioned.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
135 / 1,469,506 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.050
Open source ↗
ClinVar
6 Uncertain significance
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 ↗
All source links
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/234046/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/2-215657164-C-A?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr2-214792440-C-A?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/2-214792440-C-A
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000465.4%3Ac.221G…
- OncoKB ↗www.oncokb.org/gene/BARD1/C74F
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=125494391
- 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= 9.18676e-05; MAF= 0.00919%, 135/1469506 alleles, homozygotes = 0) and has highest observed frequency in the Ashkenazi Jewish population (AF= 0.000112284; MAF= 0.01123%, 3/26718 alleles, homozygotes = 0); grpmax FAF= 8.91e-05.
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Uncertain significance (6 clinical laboratories). (ClinVarID = 234046)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.05). REVEL score = 0.932. BayesDel score = 0.560394.
Functional
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. BARD1, a tumor suppressor involved in the DNA damage response, is altered by mutation in breast and ovarian cancers.
Somatic
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV107297670, n = 3 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.