About BARD1
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
BARD1 c.1868G>A, p.(Gly623Glu)
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: 2
Benign evidence criteria: 1
Pathogenic criteria applied · 2
PS3Moderate
PS3 · moderate
The BARD1 p.Gly623Glu variant was directly tested in a homology-directed DNA repair (HDR) reporter assay in HeLa cells. The variant showed significantly reduced HDR activity (14–19% of wild-type), classified as intermediate function. It was expressed and soluble but failed to bind BRCA1, disrupting a protein–protein interaction critical for DNA repair function. This functional evidence supports a deleterious effect on protein function.
PM2Supporting
PM2 · supporting
This variant is present at very low frequency in population databases: gnomAD v2.1 AF = 0.00119% (3/251,210 alleles), gnomAD v4.1 AF = 0.00229% (37/1,613,832 alleles), grpmax FAF = 2.233e-05. All observed frequencies are well below the 0.1% threshold for PM2 in the generic ACMG framework. No homozygotes have been observed.
Benign criteria applied · 1
BP4Supporting
BP4 · supporting
Multiple lines of computational evidence suggest no impact on the gene product. BayesDel score is 0.016 (strongly benign-leaning). SpliceAI predicts no splicing impact (max delta = 0.05). REVEL score of 0.388 is indeterminate. The preponderance of in silico evidence suggests a benign effect.
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: PS3 moderate, PM2 supporting, BP4 supporting; combination = 1 moderate + 1 supporting + 1 supporting benign, 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
37 / 1,613,832 alleles
gnomAD v4.1: 37 / 1,613,832 alleles. Recorded AF 2.29268e-05. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.19422e-05; MAF= 0.00119%, 3/251210 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 2.64275e-05; MAF= 0.00264%, 3/113518 alleles, homozygotes = 0); grpmax FAF= 7.02e-06.
gnomAD-Canada
Not available in 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
8 reported laboratory submissions
8 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.
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 Not recorded, with the data and sources behind each one.
26 criteria with recorded statuses: 3 met · 18 not met · 0 not assessed · 5 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
The BARD1 c.1868G>A (p.Gly623Glu) variant is a missense substitution classified as a variant of uncertain significance. Functional evidence from a homology-directed DNA repair assay demonstrates that this variant significantly reduces HDR activity (14–19% of wild-type) and disrupts BRCA1 binding, meeting PS3 at moderate strength (Lee et al., 2015).
The variant is absent or extremely rare in population databases (gnomAD v2.1 AF 0.00119%; v4.1 AF 0.00229%), meeting PM2 at supporting strength.
Multiple computational predictors suggest a benign effect: BayesDel score is 0.016 (benign-leaning), REVEL score is 0.388 (indeterminate), and SpliceAI predicts no splicing impact (max delta 0.05), meeting BP4 at supporting strength.
At the time of assessment, no CSPEC or VCEP framework exists for BARD1. The generic ACMG/AMP 2015 framework was applied. Combining PS3_moderate and PM2_supporting with BP4_supporting yields a net evidence profile of one moderate pathogenic criterion plus one supporting pathogenic criterion partially offset by one supporting benign criterion, resulting in an overall classification of Uncertain Significance.
ClinVar classifies this variant as Uncertain Significance (1-star, 8 clinical laboratories, ClinVar Variation ID 142123). The evidence from this independent adjudication is consistent with that classification.
No criteria match.
Met · 3
PS3 ModerateThe BARD1 p.Gly623Glu variant was directly tested in a homology-directed DNA repair (HDR) reporter assay in HeLa cells. The variant showed significantly reduced HDR activity (14–19% of wild-type), classified as intermediate function. It was expressed and soluble but failed to bind BRCA1, disrupting a protein–protein interaction critical for DNA repair function. This functional evidence supports a deleterious effect on protein function. Details ▾Hide ▴
Evidence considered
- Direct functional testing of p.Gly623Glu in HDR reporter assay (HeLa-DR cells
- siRNA depletion/rescue).
- HDR activity: 19% initially
- 14% after backbone correction — classified as intermediate (significantly different from both wild-type and null).
- G623E mutant is soluble and well-expressed but fails to bind BRCA1 by co-immunoprecipitation.
- C-terminal region of BARD1 (including G623) contributes to BRCA1 heterodimer stability and HDR function.
Still missing
- Single study
- no independent replication of the functional finding. Assay is a reporter-based system in HeLa cells
- not a direct tumor suppression model. Authors note HDR function is not yet definitively linked to clinical predisposition for BARD1.
Sources
PM2 SupportingThis variant is present at very low frequency in population databases: gnomAD v2.1 AF = 0.00119% (3/251,210 alleles), gnomAD v4.1 AF = 0.00229% (37/1,613,832 alleles), grpmax FAF = 2.233e-05. All observed frequencies are well below the 0.1% threshold for PM2 in the generic ACMG framework. No homozygotes have been observed. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: 3/251
- 210 alleles (AF = 0.00119%)
- 0 homozygotes.
- gnomAD v4.1: 37/1
- 613
- 832 alleles (AF = 0.00229%)
- grpmax FAF: 2.233e-05 (well below 0.1% threshold).
- Highest subpopulation frequency: European (non-Finnish) AF = 0.00264%.
Sources
BP4 SupportingMultiple lines of computational evidence suggest no impact on the gene product. BayesDel score is 0.016 (strongly benign-leaning). SpliceAI predicts no splicing impact (max delta = 0.05). REVEL score of 0.388 is indeterminate. The preponderance of in silico evidence suggests a benign effect. Details ▾Hide ▴
Evidence considered
- BayesDel: 0.0162 (strongly benign-leaning).
- SpliceAI max delta: 0.05 (no predicted splicing impact).
- REVEL: 0.388 (indeterminate
- does not meet pathogenic threshold).
Sources
Not met · 18 · evaluated, threshold not reached
PS2 No de novo observation (with confirmed maternity and paternity) has been reported for this variant. Details ▾Hide ▴
Evidence considered
- No de novo report identified in ClinVar submissions or literature.
Still missing
- No trio or parent-of-origin data available for this variant.
PS4 No case-control study demonstrating statistically significant enrichment of this variant in affected individuals versus controls was identified. Details ▾Hide ▴
Evidence considered
- No variant-specific case-control data available in the reviewed literature or databases.
Still missing
- Absence of variant-specific prevalence data in affected cohorts.
PM1 Gly623 is located in the C-terminal region of BARD1, which contributes to BRCA1 binding and HDR function. The G623E mutant disrupts BRCA1 binding. However, the exact domain boundaries for a well-characterized critical functional domain encompassing residue 623 are not clearly defined in the available evidence. The variant is not in a statistically significant cancer hotspot (cancerhotspots.org). While the C-terminal region is functionally important, domain-level evidence is insufficient to apply PM1 at this position. Details ▾Hide ▴
Evidence considered
- G623E disrupts BRCA1 binding and reduces HDR function.
- C-terminal region of BARD1 is important for BRCA1 heterodimer stability.
- Not in a statistically significant cancer hotspot.
Still missing
- Precise BRCT domain boundaries for BARD1 not established in the case materials
- unable to confirm G623 is within a defined critical domain.
Sources
PM6 No de novo observation (with confirmed maternity and paternity) has been reported for this variant. Details ▾Hide ▴
Evidence considered
- No de novo report identified.
Still missing
- No trio data available.
PP1 No segregation data (co-segregation with disease in multiple affected family members) is available for this variant. Details ▾Hide ▴
Evidence considered
- No family segregation studies identified.
Still missing
- No pedigree or LOD score data available.
PP2 PP2 requires that the gene has a low rate of benign missense variation and that missense variants are a common mechanism of disease. For BARD1, this has not been well established — the gene's status as a definitive HBOC susceptibility gene remains under investigation, and the rate of pathogenic versus benign missense variation is not clearly defined. Details ▾Hide ▴
Evidence considered
- BARD1 is not yet definitively classified as an HBOC susceptibility gene per Easton et al. 2015
- the proportion of pathogenic missense variants is not well characterized.
Still missing
- BARD1 gene-level PP2 eligibility has not been established in the case materials.
PP3 Multiple lines of computational evidence do not support a deleterious effect. REVEL score is 0.388 (intermediate, not meeting typical pathogenic thresholds). BayesDel score is 0.016 (strongly benign-leaning). SpliceAI predicts no significant splice impact (max delta = 0.05). The in silico evidence does not reach the threshold for PP3. Details ▾Hide ▴
Evidence considered
- REVEL: 0.388 (intermediate
- below pathogenic threshold of ~0.5).
- BayesDel: 0.0162 (strongly benign-leaning).
- SpliceAI max delta: 0.05 (no predicted splice impact).
- HCI prior: not available for BARD1.
Sources
PP4 No variant-specific phenotype data demonstrating that the patient's phenotype or family history is highly specific for BARD1-related disease has been identified for this variant. Details ▾Hide ▴
Evidence considered
- No variant-specific phenotype or clinical data available in the reviewed sources.
Still missing
- No proband phenotype data available in the case materials.
PP5 The ClinVar classification for this variant is Uncertain Significance with review status 'criteria provided, single submitter' (1-star). The global PP5 rule requires ClinVar 3-star expert panel classification to apply at supporting strength. This variant does not meet that threshold. Details ▾Hide ▴
Evidence considered
- ClinVar classification: Uncertain Significance.
- Review status: criteria provided
- single submitter (1-star).
- 8 clinical laboratories have submitted
- all classify as VUS.
Sources
BA1 The maximum population frequency of this variant (gnomAD v4.1 AF = 0.00229%) is far below the 1% threshold for BA1 in the generic ACMG framework. Details ▾Hide ▴
Evidence considered
- Maximum AF: 0.00229% (gnomAD v4.1)
- well below 1% BA1 threshold.
Sources
BS1 The maximum population frequency of this variant (gnomAD v4.1 AF = 0.00229%) is below the 0.3% threshold for BS1 in the generic ACMG framework. Details ▾Hide ▴
Evidence considered
- Maximum AF: 0.00229% (gnomAD v4.1)
- below 0.3% BS1 threshold.
Sources
BS2 No evidence that this variant has been observed in a healthy adult individual for a fully penetrant disorder with clear dominant inheritance. Details ▾Hide ▴
Evidence considered
- No observation in confirmed healthy controls for a fully penetrant BARD1-associated disorder.
Still missing
- Penetrance of BARD1-associated disease is not well characterized
- no healthy control data available for this variant.
BS3 The well-established functional study (Lee et al., 2015, PMID:26350354) directly tested p.Gly623Glu and demonstrated significantly reduced HDR function (14–19% of wild-type). The variant was classified as intermediate — not normal/functional. This functional evidence does NOT support a benign effect; rather it supports a deleterious effect. Details ▾Hide ▴
Evidence considered
- G623E showed 14–19% HDR activity (intermediate
- not functional).
- G623E failed to bind BRCA1 by co-immunoprecipitation.
- Functional data contradicts BS3 (no deleterious effect).
Sources
BS4 No segregation data (lack of co-segregation with disease in affected family members) is available for this variant. Details ▾Hide ▴
Evidence considered
- No family segregation studies identified.
Still missing
- No segregation data available.
BP1 BP1 requires that the gene has a primary truncating mechanism and that missense variants are not a known cause of disease. BARD1 has known pathogenic missense variants (e.g., in the RING domain) that disrupt BRCA1 binding and HDR function. Therefore BP1 does not apply. Details ▾Hide ▴
Evidence considered
- BARD1 missense variants in the RING domain (p.C53W
- p.C71Y
- p.L44R) are defective in HDR and disrupt BRCA1 binding.
- Pathogenic missense variants are a known mechanism in BARD1.
Sources
BP2 No observation of this variant in trans with a known pathogenic BARD1 variant has been reported. Details ▾Hide ▴
Evidence considered
- No observation in trans with a pathogenic variant.
Still missing
- No phase data available.
BP6 The ClinVar classification for this variant is Uncertain Significance with review status 'criteria provided, single submitter' (1-star). The global BP6 rule requires ClinVar 3-star expert panel benign/likely benign classification to apply at supporting strength. This variant does not meet that threshold. Details ▾Hide ▴
Evidence considered
- ClinVar classification: Uncertain Significance.
- Review status: criteria provided
- single submitter (1-star).
Sources
PS5 No evidence that this specific nucleotide change (c.1868G>A) has been previously established as a pathogenic variant in any context. Details ▾Hide ▴
Evidence considered
- Variant is classified as Uncertain Significance in ClinVar
- no prior pathogenic assertion for this exact nucleotide change.
Not applicable · 5· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANM_000465.4:c.1868G>A is a missense variant (p.Gly623Glu). It does not fall into the generic PVS1 null-variant buckets of nonsense, frameshift, or canonical ±1,2 splice consensus variants per ClinGen SVI PVS1 recommendations (PMC6185798). Details ▾Hide ▴
Evidence considered
- Variant is a missense substitution
- not a predicted null variant.
Sources
PS1 N/ANo previously established pathogenic missense variant at the same amino acid position with a different nucleotide change was identified for BARD1 Gly623. Details ▾Hide ▴
No further detail was recorded.
PM5 N/ANo same-residue comparator variants with expert-panel pathogenic classification could be identified for automated PM5 candidate harvesting. Details ▾Hide ▴
Evidence considered
- PM5 candidate search returned no qualifying comparators.
Sources
pm5_candidates
BP5 N/ANo alternate molecular basis for disease has been identified in the case materials that would make this variant less likely to be causative. Details ▾Hide ▴
No further detail was recorded.
BP7 N/ABP7 applies to synonymous variants where splicing prediction algorithms predict no impact. NM_000465.4:c.1868G>A is a missense variant (p.Gly623Glu), not a synonymous variant. Details ▾Hide ▴
Evidence considered
- Variant is a missense substitution
- not synonymous.
Identifiers
- Gene
- BARD1
- Transcript
- NM_000465.4
- Coding (HGVS c.)
- NM_000465.4:c.1868G>A
- Protein (HGVS p.)
- NP_000456.2:p.(Gly623Glu)
- GRCh38
- chr2:214745102 C>T
- GRCh37
- chr2:215609826 C>T
- ClinVar
- 2057879, 142123
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
37 / 1,613,832 alleles
AF 2.29e-05 · 0 homozygotes · FAF 2.23e-05
gnomAD v2.1
3 / 251,210 alleles
AF 1.19e-05 · 0 homozygotes · FAF 7.02e-06
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 2.3e-05 · 37 / 1,613,832 alleles · 0 hom · FAF 2.2e-05
| European (non-Finnish)36 / 1,179,966 | 3.1e-05 |
| South Asian1 / 91,072 | 1.1e-05 |
0 alternate alleles recorded in 8 other groups: Remaining individuals, Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, Ashkenazi Jewish, African/African American.
gnomAD v2.1
AF 1.2e-05 · 3 / 251,210 alleles · 0 hom · FAF 7e-06
| European (non-Finnish)3 / 113,518 | 2.6e-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= 2.29268e-05; MAF= 0.00229%, 37/1613832 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 3.05094e-05; MAF= 0.00305%, 36/1179966 alleles, homozygotes = 0); grpmax FAF= 2.233e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.19422e-05; MAF= 0.00119%, 3/251210 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 2.64275e-05; MAF= 0.00264%, 3/113518 alleles, homozygotes = 0); grpmax FAF= 7.02e-06.
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.388
- BayesDel
- 0.016
How the predictions were used
BP4 SupportingMultiple lines of computational evidence suggest no impact on the gene product. BayesDel score is 0.016 (strongly benign-leaning). SpliceAI predicts no splicing impact (max delta = 0.05). REVEL score of 0.388 is indeterminate. The preponderance of in silico evidence suggests a benign effect. Details ▾Hide ▴
Evidence considered
- BayesDel: 0.0162 (strongly benign-leaning).
- SpliceAI max delta: 0.05 (no predicted splicing impact).
- REVEL: 0.388 (indeterminate
- does not meet pathogenic threshold).
Sources
PP3 Multiple lines of computational evidence do not support a deleterious effect. REVEL score is 0.388 (intermediate, not meeting typical pathogenic thresholds). BayesDel score is 0.016 (strongly benign-leaning). SpliceAI predicts no significant splice impact (max delta = 0.05). The in silico evidence does not reach the threshold for PP3. Details ▾Hide ▴
Evidence considered
- REVEL: 0.388 (intermediate
- below pathogenic threshold of ~0.5).
- BayesDel: 0.0162 (strongly benign-leaning).
- SpliceAI max delta: 0.05 (no predicted splice impact).
- HCI prior: not available for BARD1.
Sources
BP7 N/ABP7 applies to synonymous variants where splicing prediction algorithms predict no impact. NM_000465.4:c.1868G>A is a missense variant (p.Gly623Glu), not a synonymous variant. Details ▾Hide ▴
Evidence considered
- Variant is a missense substitution
- not synonymous.
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.05). REVEL score = 0.388. BayesDel score = 0.0162055.
8 paper records listed. 1 cited in the classification.
Cited in the classification
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PMID 26350354 ↗Functional Analysis of BARD1 Missense Variants in Homology-Directed Repair of DNA Double Strand Breaks.Lee C et al. · 2015 DecLee et al. (2015) tested 29 BARD1 missense variants for homology-directed DNA repair (HDR) function in a HeLa cell reporter assay. The p.Gly623Glu variant showed significantly reduced HDR activity (14–19% of wild-type), classified as intermediate function. The mutant protein was soluble and well-expressed but failed to bind BRCA1 by co-immunoprecipitation, indicating disruption of a C-terminal protein–protein interaction critical for DNA repair.→ PS3 Names this variant
Source detail
The lack of binding of the p.G623E mutant confirms that the C-terminus of BARD1 contributes to BRCA1 binding.
Location Table 1 (variant listing); Results, paragraphs on HDR assay and expression analysis; Figure 1C; Figure 3 (corrected backbone); Figure 4 (BRCA1 co-IP); Discussion.
Context HDR reporter assay (GFP-based), HeLa-DR-13-9 cells; siRNA depletion of endogenous BARD1 followed by plasmid rescue; co-immunoprecipitation for BRCA1 binding; immunoblot for protein expression.
Other recorded publications
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PMID 17508274 ↗Risk assessment and genetic counseling for hereditary breast and ovarian cancer:Berliner and Fay (2007) provide practice recommendations from the National Society of Genetic Counselors for hereditary breast and ovarian cancer risk assessment and genetic counseling. This is a clinical practice guideline focused on BRCA1 and BRCA2; BARD1 and the specific variant NM_000465.4:c.1868G>A are not discussed.Does not name this variant
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PMID 20301425 ↗BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer.Adam MP et al. · 1993No 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. · 2015Hampel et al. (2014) present ACMG and NSGC joint practice guidelines for cancer predisposition referral indications. This is a clinical referral guideline covering multiple hereditary cancer syndromes. BARD1 and the variant NM_000465.4:c.1868G>A are not discussed.Does not name this variant
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PMID 25741868 ↗Standards and guidelines for the interpretation of sequence variants: a joint coRichards et al. (2015) present the ACMG/AMP standards and guidelines for interpretation of sequence variants. This is the foundational framework document describing the five-tier classification system and evidence criteria. BARD1 and the specific variant NM_000465.4:c.1868G>A are not discussed.Does not name this variant
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PMID 26389210 ↗Genetics of Breast and Gynecologic Cancers (PDQ®): Health Professional Version.No paper-specific finding is recorded.
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PMID 26467025 ↗A Standardized DNA Variant Scoring System for Pathogenicity Assessments in MendeKarbassi et al. (2015) describe a standardized DNA variant scoring system for pathogenicity assessments used at Quest Diagnostics. The paper summarizes 16,500 pathogenicity assessments across 338 genes but does not discuss the specific BARD1 variant NM_000465.4:c.1868G>A.Does not name this variant
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PMID 27498913 ↗Monogenic and polygenic determinants of sarcoma risk: an international genetic study.Ballinger ML et al. · 2016No paper-specific finding is recorded.
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
37 / 1,613,832 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
8 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/142123/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/2-215609826-C-T?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr2-214745102-C-T?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/2-214745102-C-T
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000465.4%3Ac.1868…
- OncoKB ↗www.oncokb.org/gene/BARD1/G623E
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=BARD1+c.1868G%3EA
- 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= 2.29268e-05; MAF= 0.00229%, 37/1613832 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 3.05094e-05; MAF= 0.00305%, 36/1179966 alleles, homozygotes = 0); grpmax FAF= 2.233e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.19422e-05; MAF= 0.00119%, 3/251210 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 2.64275e-05; MAF= 0.00264%, 3/113518 alleles, homozygotes = 0); grpmax FAF= 7.02e-06.
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Uncertain significance (8 clinical laboratories). (ClinVarID = 142123)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.05). REVEL score = 0.388. BayesDel score = 0.0162055.
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 not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.