Skip to main content
Public beta This website is in public beta – please give your feedback.
Genes

BARD1

BARD1 (BRCA1-associated RING domain) is a tumour suppressor gene. It is associated with moderately increased breast cancer risks, which are dependent on variant type, family history and other lifestyle/reproductive risk factors.

Gene function

BARD1 maintains genomic stability by functioning in DNA repair, ubiquitination and transcriptional regulation.

The BRCA1-BARD1 complex functions in the homologous recombination DNA repair pathway that repairs DNA double-strand breaks by assisting in the recruitment of RAD51 to the single-stranded DNA as a template for repair and downstream pathway function.

Gene locus and structure

BARD1 is located on chromosome 2, and is composed of 11 exons. It is composed of a highly conserved, single N-terminal RING and two C-terminal BRCT (BRCA-1 C terminus) domains, similar to BRCA1. However, BARD1 also has four tandem ANK (ankyrin repeat) domains adjacent to the BRCT domains.

Prevalence

The population frequency of likely pathogenic and pathogenic variants in BARD1 is thought to be approximately 0.1% in non-Finnish European populations. A rare founder variant, BARD1 c.1935_1954dup, has been identified in the non-Finnish European population.

Pathogenic variant spectrum

The majority of variants in BARD1 are sequence variants involving single nucleotides, but larger deletions and duplications have been reported.

Disease associations

There is strong evidence that constitutional (likely) pathogenic variants in BARD1 predispose to breast cancer. The cancer risks associated with pathogenic BARD1 variants are variant type-specific, with protein truncating variants (PTV) associated with higher risks than missense variants (see odds ratios below).

The variant type-specific BARD1-associated female breast cancer risks are:

  • Truncating variants: odds ratio (OR) 2.09 (95% confidence interval (CI) 1.35-3.23)
  • Missense variants: OR 1 (95% CI 0.89-1.1)

Of note, BARD1 c.1935_1954dup (p.Glu652fs) is a recurrent and reportable variant. Case:control data from UK Biobank indicates an associated risk similar or exceeding that of GPV: OR 3.25 (95% CI 1.79-5.89)

The lifetime risk of breast cancer is estimated to be 17%–30%, but associated risks are greatly modified by variant type, and may be further modified by lifestyle and/or environmental factors.

Variants in BARD1 predispose mainly to triple negative breast cancer, and constitutional (germline) pathogenic variants (GPV) in BARD1 are present in 0.41%–0.9% of patients with triple negative breast cancer (TNBC).

Current data does not support a strong association between ovarian cancer and BARD1 GPVs. The risk of other cancers with BARD1 GPVs is uncertain.

BARD1 GPVs have been rarely identified in male patients with breast cancer. Associated risk estimates are uncertain, confidence intervals wide, and risks have not yet been stratified by variant type. Emerging evidence from Queen’s University suggests OR 3.55 (CI 0.90–10.13).

Genomic testing

The clinical phenotype associated with pathogenic and likely pathogenic variants in BARD1 may be clinically indistinguishable from that associated with likely pathogenic and pathogenic variants in ATM, BRCA1, BRCA2, PALB2, RAD51C, RAD51D or CHEK2. For this reason, testing of all these genes is typically undertaken simultaneously as part of a small panel for eligible patients.

Constitutional (germline) genomic testing of BARD1 is available through the National Genomic Test Directory for individuals affected by breast cancer who meet the eligibility criteria, under test code R208 (Inherited breast cancer and ovarian cancer).

In the NHS, analysis and reporting of variants in BARD1 is restricted to those associated with higher risk, and includes BARD1 c.1935_1954dup (p.Glu652fs) OR 3.25 (95% CI 1.79-5.89) as a reportable exception variant.

Referral to clinical genetics may be considered for those individuals with uninformative breast cancer susceptibility gene panel testing if clinical suspicion of an underlying hereditary risk factor remains high, as further testing may be indicated, for example, for syndromic predisposition or rare mechanisms of disease.

Genomic counselling

BARD1-associated cancer risk is inherited in an autosomal dominant pattern.

First-degree relatives of an individual with a likely pathogenic or pathogenic variant in BARD1 have a 50% chance of having the familial variant.

Referral of affected patients to clinical genetics should be arranged to discuss onward management, family planning implications and cascade testing of at-risk relatives. All carriers of GPVs in BARD1 should also be enrolled to the National Inherited Cancer Predisposition Register (NICPR) (or equivalent in devolved nations), which is currently done through clinical genetics services.

If you are discussing genomics concepts with your patients, you may find it helpful to use the visual communication aids for genomics conversations.

Risk-reducing strategies

Breast cancer management

Symptom awareness

  • All affected individuals should be provided with advice regarding symptom awareness.
Screening
  • Screening should be based on individualised risk assessment using tools such as CanRisk, and in accordance with NICE guidelines on familial breast cancer (CG164).
  • Individuals with truncating/higher risk variants in BARD1 should be offered at least moderate-risk breast screening (annual mammograms between 40 and 50 years of age, followed by population screening) but may be offered high-risk breast screening (annual mammograms between 40 and 60 years of age, followed by population screening) if the estimated lifetime risk of breast cancer, determined by family history and CanRisk estimation, is 30% or higher.
  • If an individual has had a lower risk (for example, missense variant) in BARD1 identified (for example, through private or self-funded testing), screening should be individualised and guided by family history rather than genotype. Caution should be exercised in using CanRisk to determine screening in individuals with variants of lower penetrance, given that genotype-specific calculations are not possible at present.
Role of risk reducing surgery
  • The role of risk-reducing bilateral mastectomy in individuals with likely pathogenic or pathogenic BARD1 variants is uncertain, but it may be considered for those with higher-risk variants and an estimated lifetime breast cancer risk of 30% or higher.
  • The survival advantage of surgery compared with surveillance is uncertain.
  • Contralateral prophylactic mastectomy in an individual with a BARD1 variant who has already been affected by breast cancer may be considered and, if feasible and clinically appropriate, may be undertaken at the same time as therapeutic mastectomy.
    • Contralateral prophylactic surgery will minimise the risk of a second primary breast cancer, but the risk of recurrence from the first breast cancer should be carefully considered when counselling the patient about the potential advantages of this surgery.
  • It is best practice that decisions regarding prophylactic surgery in carriers of constitutional (germline) BARD1 variants should be made only after discussion at a specialist multidisciplinary team meeting, with input from clinical genetics.
Risk-reducing medication
  • Guidance from NICE published in March 2017 recommends that risk-reducing medication with tamoxifen, raloxifene or anastrozole should be considered in women at increased risk of breast cancer based on their family history, after giving due consideration to potential contraindications and risks of adverse events.
  • However, the role of risk-reducing medication in the prevention of BARD1-associated breast cancer susceptibility has not been specifically explored. Patients should be counselled regarding the impact of risk-reducing medication related to hormone driven cancers, the enrichment of triple negative disease in carriers of BARD1 variants should be acknowledged.
Breast cancer management considerations
  • At present, treatment of breast cancer in those with heterozygous BARD1 variants is as per standard practice.
Male breast cancer risk management
  • Breast cancer risk in male carriers of BARD1 variants is uncertain, but breast cancers have been reported. Breast cancer screening is not routinely recommended in men with pathogenic BARD1 variants, but breast symptom awareness is encouraged.

Other cancers

  • At present, screening for other cancer types is not typically recommended, unless otherwise required because of a strong family history.

Family planning implications

  • Pre-implantation genetic testing for monogenic or single-gene disorders (PGT-M) is available for certain genetic conditions associated with significant health risks. PGT-M can only be used for certain conditions, after approval by the UK Fertility Regulator (The Human Fertilisation and Embryology Authority). The HFEA decides approval by assessing severity, likelihood of inheritance, and evidence from affected families. It is important to recognise that HFEA approval is not automatic for these scenarios: the Statutory Approvals Committee will require a transparent, evidence-based justification demonstrating that the variant confers a sufficiently serious and well-characterised risk to meet regulatory criteria.
  • With respect to family planning in carriers of variants associated with moderate cancer risk, decisions regarding the appropriateness of interventions such as PGT-M or prenatal testing with termination of affected embryos should be also be guided by available evidence, multidisciplinary input, and careful exploration of the family history and context.
  • Other options for family planning may include adoption, gamete donation, or natural conception and pregnancy with testing of children in adulthood.
  • Discussions regarding PGT-M and other family planning options should be undertaken by a specialist genetic counsellor or clinical geneticist.

Resources

For clinicians

References:

↑ Back to top
  • Last reviewed: 05/08/2026
  • Next review due: 05/08/2029
  • Authors: Dr David McMahon
  • Reviewers: Dr Terri McVeigh