About BARD1
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
BARD1 c.1217G>A, p.(Arg406Gln)
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 very low frequency in population databases: gnomAD v2.1 allele frequency 0.006% (17/282,356 alleles, 0 homozygotes) and gnomAD v4.1 allele frequency 0.002% (39/1,613,954 alleles, 1 homozygote). The frequency is well below the 0.1% threshold for PM2 under generic ACMG rules. Absent from gnomAD-Canada v1.0.
Benign criteria applied · 1
BP4Supporting
BP4 · supporting
Multiple lines of computational evidence suggest no impact on gene product. REVEL score is 0.117 (benign-predicting, below 0.5 threshold). BayesDel score is -0.406678 (benign-predicting, negative value). SpliceAI max delta score is 0.05 (no predicted splicing impact, well below 0.2 threshold). All three in silico tools consistently predict 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: 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
39 / 1,613,954 alleles
gnomAD v4.1: 39 / 1,613,954 alleles. Recorded AF 2.41643e-05. Recorded homozygote count 1.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 6.02077e-05; MAF= 0.00602%, 17/282356 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 0.000451128; MAF= 0.04511%, 9/19950 alleles, homozygotes = 0); grpmax FAF= 0.00021575.
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
9 reported laboratory submissions
8 Uncertain significance · 1 Likely benign.
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
2 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV53611525, n = 2 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.
29 criteria with recorded statuses: 2 met · 12 not met · 10 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.1217G>A (p.Arg406Gln) is a missense variant in BARD1 exon 4.
This variant is present at very low frequency in population databases: gnomAD v2.1 allele frequency 0.006% (17/282,356 alleles, 0 homozygotes) and gnomAD v4.1 allele frequency 0.002% (39/1,613,954 alleles, 1 homozygote), meeting PM2 (supporting).
Multiple lines of computational evidence predict a benign effect: REVEL score 0.117, BayesDel score -0.406678, and SpliceAI max delta 0.05, meeting BP4 (supporting).
Functional studies show conflicting results: p.R406Q is fully functional in homology-directed repair (149% of wild-type activity; PMID:26350354) but shows partially impaired apoptosis in patient-derived lymphoblastoid cells (TUNEL and Annexin V assays; PMID:31371347). Neither PS3 nor BS3 is met due to inconsistent evidence across assay types.
This variant has been reported in two unrelated patients with early-onset colorectal cancer (ages 24 and 37; PMID:31371347), but colorectal cancer is not the classic BARD1-associated phenotype (hereditary breast and ovarian cancer).
In ClinVar (Variation ID 127713), this variant is classified as Uncertain Significance by 8 clinical laboratories and Likely Benign by 1 laboratory, with no expert panel review available.
No de novo, segregation, or case-control data are available. No pathogenic missense variant at the same residue has been identified (PM5 not met).
No criteria match.
Met · 2
PM2 SupportingThis variant is present at very low frequency in population databases: gnomAD v2.1 allele frequency 0.006% (17/282,356 alleles, 0 homozygotes) and gnomAD v4.1 allele frequency 0.002% (39/1,613,954 alleles, 1 homozygote). The frequency is well below the 0.1% threshold for PM2 under generic ACMG rules. Absent from gnomAD-Canada v1.0. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: AF=6.02e-05 (17/282
- 356 alleles
- 0 homozygotes)
- gnomAD v4.1: AF=2.42e-05 (39/1
- 613
- 954 alleles
- 1 homozygote)
- gnomAD-Canada: absent
- All frequencies well below 0.1% PM2 threshold
Sources
BP4 SupportingMultiple lines of computational evidence suggest no impact on gene product. REVEL score is 0.117 (benign-predicting, below 0.5 threshold). BayesDel score is -0.406678 (benign-predicting, negative value). SpliceAI max delta score is 0.05 (no predicted splicing impact, well below 0.2 threshold). All three in silico tools consistently predict a benign effect. Details ▾Hide ▴
Evidence considered
- REVEL: 0.117 (benign-predicting)
- BayesDel: -0.406678 (benign-predicting)
- SpliceAI max delta: 0.05 (no splicing impact)
Sources
Not met · 12 · evaluated, threshold not reached
PVS1 This is a missense variant (c.1217G>A, p.Arg406Gln) and does not fall into a null-variant category (nonsense, frameshift, or canonical ±1,2 splice consensus). PVS1 is not applicable to missense variants under the ClinGen SVI PVS1 framework (PMC6185798). Details ▾Hide ▴
Evidence considered
- Variant is missense (p.Arg406Gln)
- not a null variant.
Sources
PS3 Well-established functional studies do not demonstrate a consistent damaging effect. PMID:26350354 showed p.R406Q is fully functional in homology-directed repair (HDR) assay (149% of wild-type activity). PMID:31371347 reported partially impaired apoptosis in patient-derived lymphoblastoid cells (TUNEL and Annexin V assays, 0.4-0.8 fold of controls) but normal BARD1-BRCA1 colocalization and RAD51 foci formation. The functional evidence is conflicting across assays and does not meet the threshold for well-established damaging effect. Details ▾Hide ▴
Evidence considered
- HDR assay: fully functional (149% of WT) — PMID:26350354
- Apoptosis assays: partially impaired (0.4-0.8 fold) — PMID:31371347
- BRCA1 colocalization and RAD51 foci: normal — PMID:31371347
Still missing
- Conflicting functional data across assays (HDR functional vs. apoptosis impaired).
- Single study for each assay type.
- Apoptosis effect is partial
- not complete loss.
Sources
PM1 Residue 406 is not located in a statistically significant mutational hotspot, and the variant is observed in population databases (gnomAD v2.1 AF=0.006%, v4.1 AF=0.002%), indicating it is not in a critical invariant functional domain. Details ▾Hide ▴
Evidence considered
- Residue not in a statistically significant hotspot.
- Variant present in gnomAD at low frequency.
Sources
PM5 No pathogenic missense variant at the same amino acid residue (Arg406) was identified in ClinVar or the literature. The automated PM5 candidate search found no eligible comparator variants at this residue. Details ▾Hide ▴
Evidence considered
- No pathogenic missense variants at Arg406 identified.
- Automated PM5 candidate search returned no candidates.
Sources
PP3 Multiple lines of computational evidence do not support a deleterious effect. REVEL score is 0.117 (below the 0.5 threshold, predicting benign). BayesDel score is -0.406678 (negative, predicting benign). SpliceAI max delta score is 0.05 (no predicted splicing impact). All in silico tools predict a benign effect. Details ▾Hide ▴
Evidence considered
- REVEL: 0.117 (benign-predicting)
- BayesDel: -0.406678 (benign-predicting)
- SpliceAI max delta: 0.05 (no splicing impact)
Sources
PP4 The patient phenotype is not highly specific for BARD1-related disease. The two reported cases in PMID:31371347 presented with early-onset colorectal cancer (ages 24 and 37), which is not the classic BARD1-associated phenotype (hereditary breast and ovarian cancer). No patients with breast or ovarian cancer carrying this variant were identified. Details ▾Hide ▴
Evidence considered
- Two patients with colorectal cancer reported
- not breast/ovarian cancer.
- BARD1 is primarily associated with breast and ovarian cancer susceptibility.
Sources
PP5 No reputable source has classified this variant as pathogenic. In ClinVar (Variation ID 127713), 8 clinical laboratories classify it as Uncertain Significance and 1 laboratory classifies it as Likely Benign. No expert panel review is available. PMID:31371347 suggests the variant 'may be pathogenic' but explicitly states there is insufficient evidence for reclassification per ACMG criteria. Details ▾Hide ▴
Evidence considered
- ClinVar: 8 labs VUS
- 1 lab Likely Benign
- PMID:31371347: suggests may be pathogenic but states insufficient evidence for reclassification
Sources
BA1 The variant allele frequency is far below the 1% BA1 threshold. gnomAD v2.1 AF=0.006%, gnomAD v4.1 AF=0.002%. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 AF=0.006% (far below 1%)
- gnomAD v4.1 AF=0.002% (far below 1%)
Sources
BS1 The variant allele frequency is below the 0.3% BS1 threshold for non-VCEP genes. gnomAD v2.1 AF=0.006%, gnomAD v4.1 AF=0.002%. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 AF=0.006% (below 0.3%)
- gnomAD v4.1 AF=0.002% (below 0.3%)
Sources
BS3 Well-established functional studies do not consistently show no damaging effect. While PMID:26350354 demonstrated that p.R406Q is fully functional in HDR (149% of wild-type activity), PMID:31371347 reported partially impaired apoptosis in patient-derived lymphoblastoid cells. The conflicting functional evidence across different assays precludes application of BS3. Details ▾Hide ▴
Evidence considered
- HDR assay: fully functional (149% of WT) — supports benign
- Apoptosis assays: partially impaired (0.4-0.8 fold) — does not support benign
- Conflicting evidence across assay types
Still missing
- Conflicting functional data
- no single assay captures all BARD1 functions.
Sources
BP1 BARD1 is not a gene in which only truncating variants cause disease. Both missense and truncating pathogenic variants have been reported in BARD1, and functional studies of missense variants (e.g., PMID:26350354, PMID:31371347) demonstrate that missense changes can affect protein function. Details ▾Hide ▴
Evidence considered
- BARD1 has both truncating and missense pathogenic variants reported.
- Functional studies demonstrate missense variants can impact BARD1 function.
Sources
BP6 No reputable source has classified this variant as benign. In ClinVar, 8 clinical laboratories classify it as Uncertain Significance and only 1 laboratory (Ambry Genetics, SCV000275338) classifies it as Likely Benign. A single Likely Benign classification with 8 conflicting VUS classifications does not constitute a reputable source consensus for benign classification. Details ▾Hide ▴
Evidence considered
- ClinVar: 1 Likely Benign (Ambry)
- 8 VUS — no consensus for benign.
Sources
Not assessed · 10 · no assessment recorded
PS1 No evidence of a different nucleotide change at this position producing the same amino acid change (p.Arg406Gln) that has been established as pathogenic. No alternate nucleotide variants at codon 406 were identified. Details ▾Hide ▴
Still missing
- No alternate nucleotide changes at codon 406 were identified in ClinVar or the literature.
PS2 No de novo testing was performed for the two patients (L75, S490) reported in PMID:31371347. Parental samples were not analyzed. Details ▾Hide ▴
Evidence considered
- Two patients with c.1217G>A reported but no parental testing performed.
Still missing
- No de novo confirmation with parental studies.
Sources
PS4 No case-control study comparing variant prevalence in affected individuals versus controls is available. Two cases with colon cancer reported in PMID:31371347, but this is insufficient for statistical comparison. Details ▾Hide ▴
Evidence considered
- Two unrelated patients with colorectal cancer reported.
Still missing
- No case-control or cohort study with statistical power.
Sources
PM6 No de novo data are available for this variant. The two patients reported in PMID:31371347 did not undergo parental testing. Details ▾Hide ▴
PP1 No co-segregation data are available. The two patients in PMID:31371347 (L75 and S490) are unrelated, and no family testing for this variant was performed. Details ▾Hide ▴
PP2 No missense constraint Z-score or HCI prior score is available for BARD1 to assess whether the gene has a low rate of benign missense variation. HCI prior lookup returned 'gene_not_supported' for BARD1. Details ▾Hide ▴
Evidence considered
- HCI prior not available for BARD1.
Still missing
- No missense constraint metric available for BARD1.
BS2 No data are available regarding observation of this variant in healthy adults with complete ascertainment and full penetrance evaluation. Details ▾Hide ▴
Still missing
- No healthy adult observation data with full penetrance context.
BS4 No segregation data are available. Family members of the two reported patients in PMID:31371347 were not tested for this variant. Details ▾Hide ▴
Still missing
- No segregation analysis in affected families.
BP2 No data are available regarding observation of this variant in trans with a pathogenic variant for a fully penetrant dominant disorder, or in cis with a pathogenic variant. Details ▾Hide ▴
Still missing
- No phase information with other variants.
BP5 No data are available regarding an alternate molecular basis for disease in patients carrying this variant. Details ▾Hide ▴
Still missing
- No alternate molecular diagnosis reported in variant carriers.
Not applicable · 5· recorded as not applicable Show reasons ▾Hide reasons ▴
PM3 N/ASkipped per instruction — not in the assess list for this case. Details ▾Hide ▴
No further detail was recorded.
PM4 N/ASkipped per instruction — not applicable for substitution variants. Details ▾Hide ▴
No further detail was recorded.
BP3 N/ASkipped per instruction — trivially not applicable (BP3 applies to in-frame deletions/insertions in repetitive regions; this is a substitution variant). Details ▾Hide ▴
No further detail was recorded.
BP7 N/ABP7 applies to synonymous variants with no predicted splice impact. This variant (c.1217G>A, p.Arg406Gln) is a missense variant, not synonymous. Details ▾Hide ▴
No further detail was recorded.
PS5 N/APS5 is not a criterion in the ACMG/AMP 2015 guidelines (PMID:25741868). The generic ACMG framework used for this case does not include PS5. Details ▾Hide ▴
No further detail was recorded.
Identifiers
- Gene
- BARD1
- Transcript
- NM_000465.4
- Coding (HGVS c.)
- NM_000465.4:c.1217G>A
- Protein (HGVS p.)
- NP_000456.2:p.(Arg406Gln)
- GRCh38
- chr2:214780657 C>T
- GRCh37
- chr2:215645381 C>T
- ClinVar
- 127713
- COSMIC
- COSV53611525
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
39 / 1,613,954 alleles
AF 2.42e-05 · 1 homozygotes · FAF 0.000181
gnomAD v2.1
17 / 282,356 alleles
AF 6.02e-05 · 0 homozygotes · FAF 0.000216
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 2.4e-05 · 39 / 1,613,954 alleles · 1 hom · FAF 0.00018
| South Asian24 / 91,082 | 0.00026 |
| East Asian7 / 44,890 | 0.00016 |
| Remaining individuals4 / 62,478 | 6.4e-051 hom |
| African/African American1 / 74,918 | 1.3e-05 |
| European (non-Finnish)3 / 1,179,980 | 2.5e-06 |
0 alternate alleles recorded in 5 other groups: Admixed American, European (Finnish), Amish, Middle Eastern, Ashkenazi Jewish.
gnomAD v2.1
AF 6e-05 · 17 / 282,356 alleles · 0 hom · FAF 0.00022
| East Asian9 / 19,950 | 0.00045 |
| South Asian8 / 30,606 | 0.00026 |
0 alternate alleles recorded in 6 other groups: African/African American, Admixed American, Ashkenazi Jewish, European (Finnish), European (non-Finnish), Remaining individuals.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 2.41643e-05; MAF= 0.00242%, 39/1613954 alleles, homozygotes = 1) and has highest observed frequency in the South Asian population (AF= 0.000263499; MAF= 0.02635%, 24/91082 alleles, homozygotes = 0); grpmax FAF= 0.00018075.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 6.02077e-05; MAF= 0.00602%, 17/282356 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 0.000451128; MAF= 0.04511%, 9/19950 alleles, homozygotes = 0); grpmax FAF= 0.00021575.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.117
- BayesDel
- -0.407
How the predictions were used
BP4 SupportingMultiple lines of computational evidence suggest no impact on gene product. REVEL score is 0.117 (benign-predicting, below 0.5 threshold). BayesDel score is -0.406678 (benign-predicting, negative value). SpliceAI max delta score is 0.05 (no predicted splicing impact, well below 0.2 threshold). All three in silico tools consistently predict a benign effect. Details ▾Hide ▴
Evidence considered
- REVEL: 0.117 (benign-predicting)
- BayesDel: -0.406678 (benign-predicting)
- SpliceAI max delta: 0.05 (no splicing impact)
Sources
PP3 Multiple lines of computational evidence do not support a deleterious effect. REVEL score is 0.117 (below the 0.5 threshold, predicting benign). BayesDel score is -0.406678 (negative, predicting benign). SpliceAI max delta score is 0.05 (no predicted splicing impact). All in silico tools predict a benign effect. Details ▾Hide ▴
Evidence considered
- REVEL: 0.117 (benign-predicting)
- BayesDel: -0.406678 (benign-predicting)
- SpliceAI max delta: 0.05 (no splicing impact)
Sources
BP7 N/ABP7 applies to synonymous variants with no predicted splice impact. This variant (c.1217G>A, p.Arg406Gln) is a missense variant, not synonymous. Details ▾Hide ▴
No further detail was recorded.
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.05). REVEL score = 0.117. BayesDel score = -0.406678.
8 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata.
Recorded publications
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PMID 23012255 ↗ESMO Consensus Guidelines for management of patients with colon and rectal cancer. a personalized approach to clinical decision making.This paper presents ESMO Consensus Guidelines for the management of patients with colon and rectal cancer. It does not discuss BARD1 or any specific BARD1 variant. NM_000465.4:c.1217G>A was not identified in this paper.Does not name this variant
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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.This is the ACMG/AMP 2015 standards and guidelines for sequence variant interpretation. It does not discuss any specific BARD1 variant. Used only as the framework reference for criteria definitions.Does not name this variant
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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. · 2015p.R406Q (c.1217G>A) was incidentally present in the BARD1 expression plasmid backbone used for all 29 missense variant constructs. In the HDR assay, p.R406Q was fully functional at 149% of wild-type activity, classified as 'Functional' and considered a neutral variant. Correction of R406Q back to wild-type arginine in a subset of constructs did not meaningfully change results, confirming the variant does not impair homology-directed DNA repair.Names this variant
Quoted passage
Our original BARD1 expression construct had a novel p.R406Q substitution, and this version of BARD1 fully restored HDR activity to the same level as seen in cells without BARD1 inhibition... The p.R406Q missense variant has not been described in an individual and likely was the result of a change that occurred during plasmid manipulations.
Results, 'Homology-Directed Repair' section; Table 1; Figure 1C lane 19; Figure 3
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PMID 31371347 ↗Functional analysis of clinical BARD1 germline variants.Toh MR et al. · 2019c.1217G>A (p.Arg406Gln) was identified in two unrelated patients with early-onset colorectal cancer (L75: age 37, stage IVB descending colon adenocarcinoma; S490: age 24, stage IIIB transverse colon adenocarcinoma). Functional characterization in patient-derived lymphoblastoid cells showed normal BARD1-BRCA1 colocalization and normal RAD51 foci formation, but partially impaired apoptosis: TUNEL assay showed ~0.8-fold of healthy controls and Annexin V assay showed 0.4-0.7-fold of controls. The authors concluded the variant 'may be pathogenic or likely pathogenic' but explicitly stated 'there remains insufficient evidence for variant reclassification according to ACMG criteria.'Names this variant
Quoted passage
In view of deficient apoptosis, VUSs (c.1217G>A and c.1918C>A) may be pathogenic or likely pathogenic variants.
Abstract; Table 1 (Clinical Presentation); Table 2 (Variant Table); Table 3 (Functional Results); Results, 'Functional Analyses'; Discussion
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PMID 25006736 ↗Multitarget stool DNA testing for colorectal-cancer screening.Imperiale TF et al. · 2014This paper reports results of a clinical trial comparing multitarget stool DNA testing with fecal immunochemical testing for colorectal cancer screening. It does not discuss BARD1 or any BARD1 variant.Does not name this variant
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PMID 25373533 ↗Updated guidelines for biomarker testing in colorectal carcinoma: a national consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology.This paper provides updated Spanish consensus guidelines for biomarker testing in colorectal carcinoma (KRAS, NRAS, BRAF). It does not discuss BARD1 or any BARD1 variant.Does not name this variant
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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. · 2015This paper is a practice guideline from ACMG and NSGC on referral indications for cancer predisposition assessment. It does not discuss any specific BARD1 variant. NM_000465.4:c.1217G>A was not identified in this paper.Does not name this variant
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PMID 19042984 ↗National Academy of Clinical Biochemistry laboratory medicine practice guidelines for use of tumor markers in testicular, prostate, colorectal, breast, and ovarian cancers.Sturgeon CM et al. · 2008This paper provides National Academy of Clinical Biochemistry guidelines for tumor marker use in testicular, prostate, colorectal, breast, and ovarian cancers. It does not discuss BARD1 or any specific BARD1 variant.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
39 / 1,613,954 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 · 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/127713/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/2-215645381-C-T?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr2-214780657-C-T?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/2-214780657-C-T
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000465.4%3Ac.1217…
- OncoKB ↗www.oncokb.org/gene/BARD1/R406Q
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=125490674
- 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= 2.41643e-05; MAF= 0.00242%, 39/1613954 alleles, homozygotes = 1) and has highest observed frequency in the South Asian population (AF= 0.000263499; MAF= 0.02635%, 24/91082 alleles, homozygotes = 0); grpmax FAF= 0.00018075.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 6.02077e-05; MAF= 0.00602%, 17/282356 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 0.000451128; MAF= 0.04511%, 9/19950 alleles, homozygotes = 0); grpmax FAF= 0.00021575.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Uncertain significance (8 clinical laboratories) and as Likely benign (1 clinical laboratory). (ClinVarID = 127713)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.05). REVEL score = 0.117. BayesDel score = -0.406678.
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; COSV53611525, n = 2 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.