About BARD1
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
BARD1 c.1409A>G, p.(Asn470Ser)
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: 1
Benign evidence criteria: 1
Pathogenic criteria applied · 1
PM2Supporting
PM2 · supporting
This variant is present at extremely low frequency in population databases. In gnomAD v2.1, it is observed in 32 of 282,604 alleles (AF = 0.0113%; 0 homozygotes). In gnomAD v4.1, it is observed in 142 of 1,613,858 alleles (AF = 0.0088%; 0 homozygotes). The highest subpopulation frequency is in the European (Finnish) population at 0.0478% (v2.1). All frequencies are below the 0.1% threshold for PM2 under generic ACMG criteria.
Benign criteria applied · 1
BP4Supporting
BP4 · supporting
Multiple lines of computational evidence predict a benign effect for this variant. REVEL score is 0.17 (well below pathogenic thresholds), BayesDel score is -0.585 (consistent with benign), and SpliceAI predicts no splicing impact (max delta score = 0.00). The concordance of multiple in silico predictors supports a lack of functional impact.
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: PM2 supporting, BP4 supporting; combination = 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
142 / 1,613,858 alleles
gnomAD v4.1: 142 / 1,613,858 alleles. Recorded AF 8.79879e-05. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000113233; MAF= 0.01132%, 32/282604 alleles, homozygotes = 0) and has highest observed frequency in the European (Finnish) population (AF= 0.000477897; MAF= 0.04779%, 12/25110 alleles, homozygotes = 0); grpmax FAF= 8.821e-05.
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
SpliceAI score
0.000 maximum delta
Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
15 reported laboratory submissions
8 Uncertain significance · 5 Likely benign · 1 Benign · 1 likely benign. ClinVar API review status: criteria provided, conflicting classifications.
Context only
ClinVar ↗
Functional evidence
Statement recorded
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. 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
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.
29 criteria with recorded statuses: 2 met · 22 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
NM_000465.4:c.1409A>G (p.Asn470Ser) is a missense variant in exon 6 of BARD1.
This variant is present at extremely low frequency in gnomAD (v2.1: AF = 0.0113%, 32/282,604 alleles; v4.1: AF = 0.0088%, 142/1,613,858 alleles; 0 homozygotes), meeting PM2 at supporting level.
Multiple in silico tools predict a benign effect: REVEL score 0.17, BayesDel score -0.585, and SpliceAI delta score 0.00, meeting BP4 at supporting level.
The variant was reported as a putative germline mutation in 1 of 60 Japanese familial breast cancer patients and absent from 152 controls (Ishitobi et al., 2003), but this single observation is insufficient for PS4.
No variant-specific functional data exist; the functional study by Toh et al. (2019) characterized BARD1 germline variants but did not include N470S.
BARD1 is a recognized hereditary breast cancer susceptibility gene with a loss-of-function disease mechanism, consistent with tumor suppressor biology.
In ClinVar, this variant is classified as Uncertain significance (review status: criteria provided, single submitter). Multiple clinical laboratories have submitted conflicting classifications: 8 laboratories as VUS, 5 as Likely benign, and 1 as Benign.
The variant lies within the ankyrin repeat domain, a characterized protein-protein interaction domain, but the residue is not within a statistically significant mutational hotspot.
No criteria match.
Met · 2
PM2 SupportingThis variant is present at extremely low frequency in population databases. In gnomAD v2.1, it is observed in 32 of 282,604 alleles (AF = 0.0113%; 0 homozygotes). In gnomAD v4.1, it is observed in 142 of 1,613,858 alleles (AF = 0.0088%; 0 homozygotes). The highest subpopulation frequency is in the European (Finnish) population at 0.0478% (v2.1). All frequencies are below the 0.1% threshold for PM2 under generic ACMG criteria. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: AF = 0.0113% (32/282
- 604 alleles
- 0 hom).
- gnomAD v4.1: AF = 0.0088% (142/1
- 613
- 858 alleles
- Highest subpopulation AF (Finnish): 0.0478%
- still <0.1%.
- PMID:19584272: N470S showed no polymorphic variation in a cohort of 1
- 575 BRCA1 and 856 BRCA2 mutation carriers.
Sources
BP4 SupportingMultiple lines of computational evidence predict a benign effect for this variant. REVEL score is 0.17 (well below pathogenic thresholds), BayesDel score is -0.585 (consistent with benign), and SpliceAI predicts no splicing impact (max delta score = 0.00). The concordance of multiple in silico predictors supports a lack of functional impact. Details ▾Hide ▴
Evidence considered
- REVEL: 0.17 (benign range).
- BayesDel: -0.585 (benign range).
- SpliceAI: max delta = 0.00 (no predicted splicing alteration).
Sources
Not met · 22 · evaluated, threshold not reached
PS1 No prior report of a different nucleotide change at codon 470 resulting in the same amino acid substitution (p.Asn470Ser) that has been classified as pathogenic. Details ▾Hide ▴
Evidence considered
- No same-amino-acid pathogenic comparators identified.
Sources
clinvar ↗pm5_candidates
PS2 No de novo observation has been reported for NM_000465.4:c.1409A>G. Details ▾Hide ▴
Evidence considered
- No de novo data available.
Still missing
- De novo status unknown
- parental testing not available.
PS3 No variant-specific functional data exist for NM_000465.4:c.1409A>G (p.Asn470Ser). The functional study by Toh et al. (PMID:31371347) characterized other BARD1 germline variants but did not include N470S. The variant was listed in a pediatric oncology cohort table in PMID:36187937 but was not functionally tested. Details ▾Hide ▴
Evidence considered
- PMID:31371347 functionally characterized BARD1 variants but N470S was not among those tested.
- PMID:36187937 listed N470S as a VUS in a neuroblastoma patient without functional testing.
Still missing
- No experimental functional data for this variant.
Sources
PS4 The variant was observed in 1 of 60 familial breast cancer patients and absent from 152 controls (PMID:14550946), but this single observation does not provide statistically significant enrichment. No case-control study with sufficient power has been conducted. Details ▾Hide ▴
Evidence considered
- PMID:14550946: N470S found in 1/60 familial breast cancer patients vs 0/152 healthy controls
- not statistically significant.
Still missing
- No adequately powered case-control study.
Sources
PM1 The variant (p.Asn470Ser) lies within the ankyrin repeat domain of BARD1 (residues ~420-555), a characterized functional domain mediating protein-protein interactions. However, the residue is not located in a statistically significant mutational hotspot (cancerhotspots.org: residue not significant), and no cluster of pathogenic missense variants has been established specifically within the ankyrin repeat domain of BARD1. The ankyrin repeat domain crystal structure (PMID:18480049) confirms it is a structured domain, but domain-level characterization alone is insufficient for PM1 without evidence of pathogenic missense enrichment. Details ▾Hide ▴
Evidence considered
- Hotspots: residue not significant.
- PMID:16633366: Ankyrin repeat domain characterized as protein-protein interaction domain.
- No established pathogenic missense cluster in the ANK domain.
Still missing
- No established pathogenic missense mutation cluster in the BARD1 ANK domain.
Sources
PM5 No pathogenic missense variant at the same codon (Asn470) was identified in ClinVar. The PM5 candidate harvest did not identify any same-residue pathogenic comparators. Details ▾Hide ▴
Evidence considered
- pm5_candidates.json: found=false
- no same-residue pathogenic comparators identified.
Sources
pm5_candidates
PM6 No de novo observation has been reported for NM_000465.4:c.1409A>G. Details ▾Hide ▴
Evidence considered
- No de novo data available.
Still missing
- De novo status unknown.
PP1 No co-segregation data are available. The proband reported in PMID:14550946 had affected family members (mother and maternal aunt with breast cancer), but DNA from other family members was unavailable, preventing segregation analysis. Details ▾Hide ▴
Evidence considered
- PMID:14550946: Family history present but segregation analysis not possible due to unavailability of family member DNA.
Still missing
- Co-segregation analysis not performed.
Sources
PP2 No gene-level constraint data (e.g., Missense Z-score, gnomAD constraint metrics) are available in the evidence summary to assess whether BARD1 has a low rate of benign missense variation. BARD1 is a known tumor suppressor, but PP2 requires quantitative evidence of missense constraint. Details ▾Hide ▴
Evidence considered
- No constraint metrics available for BARD1 missense variation.
Still missing
- gnomAD Missense Z-score or LOEUF data not provided for BARD1.
PP3 All in silico tools predict a benign effect. REVEL score is 0.17 (below the typical 0.3-0.5 pathogenic threshold), BayesDel score is -0.585 (negative, consistent with benign), and SpliceAI delta score is 0.0 (no splicing impact). Multiple lines of computational evidence support no deleterious effect. Details ▾Hide ▴
Evidence considered
- REVEL: 0.17 (benign).
- BayesDel: -0.585 (benign).
- SpliceAI: max delta = 0.0 (no splicing impact).
Sources
PP4 Insufficient clinical phenotype data are available to determine whether the patient's presentation is highly specific for BARD1-related disease. Details ▾Hide ▴
Evidence considered
- No detailed phenotype information available in the case materials.
Still missing
- Detailed proband phenotype not provided.
PP5 ClinVar aggregate classification is Uncertain significance (review status: criteria provided, single submitter; 1-star). No 3-star expert panel has classified this variant. Under the established rules, PP5 requires a 3-star expert panel for supporting-level application. Additionally, 6 of 17 submissions classify the variant as Likely benign or Benign. Details ▾Hide ▴
Evidence considered
- ClinVar aggregate: VUS
- review status: 1-star.
- Multiple submitters classify as Likely benign (n=5) or Benign (n=1).
- No expert panel review.
Sources
BA1 The allele frequency in gnomAD is 0.0113% (v2.1) and 0.0088% (v4.1), both far below the 1% threshold for BA1. Details ▾Hide ▴
Evidence considered
- gnomAD maximum AF: 0.0478% (Finnish subpopulation) << 1% BA1 threshold.
Sources
BS1 The allele frequency in gnomAD is 0.0113% (v2.1) and 0.0088% (v4.1), below the 0.3% threshold for BS1. The highest subpopulation frequency is 0.0478% (Finnish, v2.1), still well below 0.3%. Details ▾Hide ▴
BS2 No data are available on observation of this variant in a healthy adult at an age when full penetrance of BARD1-related disease would be expected. Details ▾Hide ▴
Evidence considered
- No healthy adult observation data with appropriate age assessment.
Still missing
- No healthy adult carrier data.
BS3 No well-established functional studies have demonstrated that NM_000465.4:c.1409A>G (p.Asn470Ser) has no deleterious effect. The only functional study of BARD1 germline variants (PMID:31371347) did not include N470S among the variants tested. Details ▾Hide ▴
Evidence considered
- PMID:31371347: Functional study of BARD1 variants did not include N470S.
Still missing
- No benign functional data specific to this variant.
Sources
BS4 No non-segregation data are available for this variant. Details ▾Hide ▴
Evidence considered
- No segregation data available.
Still missing
- Segregation analysis not performed.
BP1 BP1 applies to missense variants in genes where the primary disease mechanism involves truncating variants. BARD1-associated disease involves both truncating and missense pathogenic variants (e.g., RING domain missense variants that disrupt BRCA1 binding), so BARD1 is not a gene where only truncating variants cause disease. Details ▾Hide ▴
Evidence considered
- BARD1 has known pathogenic missense variants (e.g.
- in the RING domain).
- Disease mechanism is not exclusively truncating.
Sources
BP2 No observation of this variant in trans with a known pathogenic BARD1 variant has been reported. Details ▾Hide ▴
Evidence considered
- No trans observation available.
BP5 No alternate molecular basis for disease has been identified in a case harboring this variant. Details ▾Hide ▴
Evidence considered
- No alternate molecular basis identified.
Still missing
- Alternate molecular diagnosis not excluded.
BP6 Although 6 of 17 ClinVar submissions classify this variant as Likely benign (n=5) or Benign (n=1), the aggregate ClinVar classification remains Uncertain significance with a 1-star review status. Under the established rules, BP6 requires a 3-star expert panel classification for application at supporting level. No expert panel has reviewed this variant. Details ▾Hide ▴
Evidence considered
- ClinVar aggregate: VUS (1-star).
- 6/17 submissions are benign/likely benign
- but no expert panel review.
Still missing
- No expert panel review.
Sources
PS5 This variant is not established as pathogenic by any reputable source. The ClinVar aggregate classification is Uncertain significance with a single-submitter review status. Details ▾Hide ▴
Evidence considered
- ClinVar aggregate: VUS (8 labs)
- Likely benign (5 labs)
- Benign (1 lab). No expert panel review.
Sources
Not applicable · 5· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANM_000465.4:c.1409A>G (p.Asn470Ser) is a missense variant in exon 6 of BARD1. It does not fall into the default generic PVS1 null-variant buckets (nonsense, frameshift, or canonical ±1,2 splice consensus). Generic PVS1 framework is not applicable for this variant type. Details ▾Hide ▴
Evidence considered
- Missense variant
- null-variant PVS1 criteria are not applicable.
Sources
pvs1_variant_assessment
PM3 N/APM3 applies to recessive disorders where a variant is detected in trans with a pathogenic variant; BARD1-related disease is autosomal dominant. Details ▾Hide ▴
No further detail was recorded.
PM4 N/APM4 applies to non-frameshift insertions/deletions or stop-loss variants; this is a single nucleotide substitution. Details ▾Hide ▴
No further detail was recorded.
BP3 N/ABP3 applies to in-frame deletions/insertions in repetitive regions; this is a single nucleotide substitution. Details ▾Hide ▴
No further detail was recorded.
BP7 N/ANM_000465.4:c.1409A>G is a missense variant resulting in p.Asn470Ser. BP7 applies only to synonymous variants with no predicted splice impact. Details ▾Hide ▴
Evidence considered
- Missense variant
- BP7 is specific to synonymous changes.
Identifiers
- Gene
- BARD1
- Transcript
- NM_000465.4
- Coding (HGVS c.)
- NM_000465.4:c.1409A>G
- Protein (HGVS p.)
- NP_000456.2:p.(Asn470Ser)
- GRCh38
- chr2:214767641 T>C
- GRCh37
- chr2:215632365 T>C
- ClinVar
- 141739
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
142 / 1,613,858 alleles
AF 8.8e-05 · 0 homozygotes · FAF 0.000134
gnomAD v2.1
32 / 282,604 alleles
AF 0.000113 · 0 homozygotes · FAF 8.82e-05
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 8.8e-05 · 142 / 1,613,858 alleles · 0 hom · FAF 0.00013
| European (Finnish)42 / 63,990 | 0.00066 |
| Middle Eastern3 / 6,082 | 0.00049 |
| Admixed American8 / 59,986 | 0.00013 |
| Remaining individuals5 / 62,474 | 8e-05 |
| European (non-Finnish)82 / 1,179,948 | 6.9e-05 |
| African/African American1 / 74,900 | 1.3e-05 |
| South Asian1 / 91,084 | 1.1e-05 |
0 alternate alleles recorded in 3 other groups: Amish, East Asian, Ashkenazi Jewish.
gnomAD v2.1
AF 0.00011 · 32 / 282,604 alleles · 0 hom · FAF 8.8e-05
| European (Finnish)12 / 25,110 | 0.00048 |
| Remaining individuals2 / 7,208 | 0.00028 |
| Admixed American4 / 35,374 | 0.00011 |
| European (non-Finnish)13 / 129,016 | 0.0001 |
| South Asian1 / 30,610 | 3.3e-05 |
0 alternate alleles recorded in 3 other groups: African/African American, Ashkenazi Jewish, East Asian.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 8.79879e-05; MAF= 0.00880%, 142/1613858 alleles, homozygotes = 0) and has highest observed frequency in the European (Finnish) population (AF= 0.000656353; MAF= 0.06564%, 42/63990 alleles, homozygotes = 0); grpmax FAF= 0.0001336.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000113233; MAF= 0.01132%, 32/282604 alleles, homozygotes = 0) and has highest observed frequency in the European (Finnish) population (AF= 0.000477897; MAF= 0.04779%, 12/25110 alleles, homozygotes = 0); grpmax FAF= 8.821e-05.
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.170
- BayesDel
- -0.585
How the predictions were used
BP4 SupportingMultiple lines of computational evidence predict a benign effect for this variant. REVEL score is 0.17 (well below pathogenic thresholds), BayesDel score is -0.585 (consistent with benign), and SpliceAI predicts no splicing impact (max delta score = 0.00). The concordance of multiple in silico predictors supports a lack of functional impact. Details ▾Hide ▴
Evidence considered
- REVEL: 0.17 (benign range).
- BayesDel: -0.585 (benign range).
- SpliceAI: max delta = 0.00 (no predicted splicing alteration).
Sources
PP3 All in silico tools predict a benign effect. REVEL score is 0.17 (below the typical 0.3-0.5 pathogenic threshold), BayesDel score is -0.585 (negative, consistent with benign), and SpliceAI delta score is 0.0 (no splicing impact). Multiple lines of computational evidence support no deleterious effect. Details ▾Hide ▴
Evidence considered
- REVEL: 0.17 (benign).
- BayesDel: -0.585 (benign).
- SpliceAI: max delta = 0.0 (no splicing impact).
Sources
BP7 N/ANM_000465.4:c.1409A>G is a missense variant resulting in p.Asn470Ser. BP7 applies only to synonymous variants with no predicted splice impact. Details ▾Hide ▴
Evidence considered
- Missense variant
- BP7 is specific to synonymous changes.
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.17. BayesDel score = -0.584707.
9 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata.
Recorded publications
-
PMID 16633366 ↗Is there more to BARD1 than BRCA1?Irminger-Finger I et al. · 2006This review article on BARD1 structure and function lists N470S among reported BARD1 mutations (Figure 1b) and describes it as a germline mutation identified in a Japanese familial breast cancer study. The paper characterizes the domain architecture of BARD1 including the ankyrin repeat domain (residues ~420-555) and its role in protein-protein interactions.Names this variant
Quoted passage
N470S, which was identified as a germline mutation14.
Figure 1b (mutation map); main text section 'BARD1 mutations and cancer'
-
PMID 18480049 ↗Crystal structure of the BARD1 ankyrin repeat domain and its functional consequences.Fox D 3rd et al. · 2008No paper-specific finding is recorded.
-
PMID 19584272 ↗Modification of ovarian cancer risk by BRCA1/2-interacting genes in a multicenter cohort of BRCA1/2 mutation carriers.Rebbeck TR et al. · 2009This study evaluated genetic modifiers of ovarian cancer risk in BRCA1/2 mutation carriers by genotyping SNPs in BARD1 and other BRCA1/2-interacting genes. Among the non-synonymous SNPs tested in BARD1, N470S showed no polymorphic variation in the cohort (i.e., the variant allele was not detected in the study population of 1,575 BRCA1 and 856 BRCA2 mutation carriers).Names this variant
Quoted passage
No polymorphic variation was detected in a number of SNPs reported in HapMap data and genotyped here, including K312N, R658C, N470S, Q564H, N295S in BARD1
Results section; nsSNP Analysis paragraph
-
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.This is the ACMG/AMP standards and guidelines paper that defines the variant classification framework. It does not discuss any specific variant, including NM_000465.4:c.1409A>G.Does not name this variant
-
PMID 30374176 ↗Outcomes of 92 patient-driven family studies for reclassification of variants of uncertain significance.This study reports outcomes of 92 patient-driven family studies for VUS reclassification across multiple genes. BARD1 c.1409A>G (p.Asn470Ser) was not among the specific variants analyzed in this study.Does not name this variant
-
PMID 31371347 ↗Functional analysis of clinical BARD1 germline variants.Toh MR et al. · 2019Toh et al. functionally characterized selected BARD1 germline pathogenic variants (c.1891_1892del, c.1935_1954dup) using patient-derived lymphoblastoid cells, assessing HR function, RAD51 foci formation, and sensitivity to DNA-damaging agents. NM_000465.4:c.1409A>G (p.Asn470Ser) was not among the variants included in this functional characterization.Does not name this variant
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PMID 36187937 ↗BRCA1-associated RING domain-1 (BARD1) loss and GBP1 expression enhance sensitivity to DNA damage in Ewing sarcoma.This study on BARD1 loss and GBP1 expression in Ewing sarcoma includes a landscape analysis of germline BARD1 variants in pediatric oncology patients. NM_000465.4:c.1409A>G (p.N470S) is listed in Table 1 as a variant of uncertain significance identified in a neuroblastoma patient (PEDS-MiONCOseq dataset). The variant was not functionally characterized; the study's experimental work focused on a different BARD1 frameshift variant (c.176_177AG; p.E59Afs*8) in the RING domain.Names this variant
Quoted passage
Neuroblastoma chr2:215632365 Missense c.1409A>G p.N470S 51% NO
Table 1 (pediatric BARD1 variant landscape); Results section 'The Landscape of Germline BARD1 Variants in Pediatric Oncology'
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PMID 14550946 ↗Mutational analysis of BARD1 in familial breast cancer patients in Japan.N470S (Asn/Ser 470, c.1482 A to G) was identified in 1 of 60 Japanese familial breast cancer patients who were negative for BRCA1/2 mutations and was absent from 152 healthy controls. The variant was reported as a putative germline mutation. No segregation analysis was possible due to unavailability of family member DNA.Names this variant
Quoted passage
we have found one novel germline mutation (Asn/Ser 470). Since such a mutation was not observed in any of 152 healthy controls, it is suggested that Asn/Ser 470 could be a germline mutation causing breast cancer.
Abstract lines 13-15; Results section 3.1; Table 2; Discussion paragraph 4
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PMID 28492532 ↗Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.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
142 / 1,613,858 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.000
Open source ↗
ClinVar
8 Uncertain significance · 5 Likely benign · 1 Benign · 1 likely benign
Open source ↗
COSMIC
Captured COSMIC source record
Open source ↗
Cancer hotspots
Captured Cancer Hotspots source record
Open source ↗
OncoKB
Captured OncoKB source record
Open source ↗
All source links
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/141739/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/2-215632365-T-C?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr2-214767641-T-C?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/2-214767641-T-C
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000465.4%3Ac.1409…
- OncoKB ↗www.oncokb.org/gene/BARD1/N470S
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=BARD1+c.1409A%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= 8.79879e-05; MAF= 0.00880%, 142/1613858 alleles, homozygotes = 0) and has highest observed frequency in the European (Finnish) population (AF= 0.000656353; MAF= 0.06564%, 42/63990 alleles, homozygotes = 0); grpmax FAF= 0.0001336.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000113233; MAF= 0.01132%, 32/282604 alleles, homozygotes = 0) and has highest observed frequency in the European (Finnish) population (AF= 0.000477897; MAF= 0.04779%, 12/25110 alleles, homozygotes = 0); grpmax FAF= 8.821e-05.
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Uncertain significance (8 clinical laboratories) and as Likely benign (5 clinical laboratories) and as Benign (1 clinical laboratory) and as likely benign (1 clinical laboratory). (ClinVarID = 141739)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.17. BayesDel score = -0.584707.
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.