BARD1-related cancer predisposition

Summary

BARD1-related cancer predisposition (MONDO:0700267) is a cancer caused by BARD1 (GenCC Definitive), with 1 cohort gene (1 CIViC-evidence somatic driver; 112 ClinVar predisposition records).

At a glance

• Classification: Cancer
• Causal gene: BARD1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 112

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	BARD1-related cancer predisposition
Mondo ID	MONDO:0700267
GARD	0026407
Is cancer (heuristic)	yes

Data availability: 112 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary neoplastic syndrome › BARD1-related cancer predisposition

Related subtypes (116): mosaic variegated aneuploidy syndrome, tuberous sclerosis, hereditary breast ovarian cancer syndrome, hereditary multiple osteochondromas, nevoid basal cell carcinoma syndrome, leukemia, chronic lymphocytic, susceptibility to, 2, blue rubber bleb nevus, cherubism, Beckwith-Wiedemann syndrome, multiple self-healing squamous epithelioma, erythroleukemia, familial, susceptibility to, goiter, multinodular 1, with or without Sertoli-Leydig cell tumors, hyperparathyroidism 2 with jaw tumors, Kaposi sarcoma, susceptibility to, hereditary leiomyomatosis and renal cell cancer, susceptibility to uveal melanoma, melanoma and neural system tumor syndrome, nasopharyngeal carcinoma, susceptibility to, 2, WAGR syndrome, neuroblastoma, susceptibility to, 1, Rothmund-Thomson syndrome, mismatch repair cancer syndrome 1, Wiskott-Aldrich syndrome, N syndrome, hereditary thrombocytopenia and hematologic cancer predisposition syndrome, prostate cancer/brain cancer susceptibility, Brooke-Spiegler syndrome, pancreatic cancer, susceptibility to, 1, Carney-Stratakis syndrome, nasopharyngeal carcinoma, susceptibility to, 1, ovarian cancer, susceptibility to, 1, colorectal cancer, susceptibility to, 1, lung cancer susceptibility 1, leukemia, chronic lymphocytic, susceptibility to, 1, Kostmann syndrome, colorectal cancer, susceptibility to, 2, colorectal cancer, susceptibility to, 3, colorectal cancer, susceptibility to, 5, colorectal cancer, susceptibility to, 6, colorectal cancer, susceptibility to, 7, leukemia, chronic lymphocytic, susceptibility to, 3, leukemia, chronic lymphocytic, susceptibility to, 4, leukemia, chronic lymphocytic, susceptibility to, 5, lung cancer susceptibility 3, colorectal cancer, susceptibility to, 8, colorectal cancer, susceptibility to, 9, colorectal cancer, susceptibility to, 10, colorectal cancer, susceptibility to, 11, lung cancer susceptibility 4, neuroblastoma, susceptibility to, 3, neuroblastoma, susceptibility to, 4, neuroblastoma, susceptibility to, 5, neuroblastoma, susceptibility to, 6, leukemia, acute lymphocytic, susceptibility to, 1, leukemia, acute lymphocytic, susceptibility to, 2, lung cancer susceptibility 5, BAP1-related tumor predisposition syndrome, familial cutaneous telangiectasia and oropharyngeal predisposition cancer syndrome, Maffucci syndrome, basal cell carcinoma, susceptibility to, 7, colorectal cancer, susceptibility to, 12, leukemia, acute lymphoblastic, susceptibility to, 3, cholangiocarcinoma, susceptibility to, progeroid features-hepatocellular carcinoma predisposition syndrome, neuroblastoma, susceptibility to, 7, DDX41-related hematologic malignancy predisposition syndrome, nasopharyngeal carcinoma, susceptibility to, 3, familial isolated hyperparathyroidism, intestinal polyposis syndrome, dyskeratosis congenita, familial rhabdoid tumor, multiple endocrine neoplasia, hereditary pheochromocytoma-paraganglioma, PTEN hamartoma tumor syndrome, familial multiple fibrofolliculoma, hereditary retinoblastoma, familial atypical multiple mole melanoma syndrome, hereditary nonpolyposis colon cancer, Li-Fraumeni syndrome, Cobb syndrome, neurofibromatosis, susceptibility to familial cutaneous melanoma, pancreatic cancer, susceptibility to, 5, leukemia, acute myeloid, susceptibility to, diffuse gastric and lobular breast cancer syndrome with or without cleft lip and/or palate, glioma susceptibility, hemangioma, capillary infantile, susceptibility to, CDH1-related diffuse gastric and lobular breast cancer syndrome, NTHL1-deficiency tumor predisposition syndrome, SAMD9-related spectrum and myeloid neoplasm risk, neuroblastoma, susceptibility to, 2, BRCA1-related cancer predisposition, BRCA2-related cancer predisposition, ATM-related cancer predisposition, CHEK2-related cancer predisposition, PALB2-related cancer predisposition, RAD51C-related cancer predisposition, RAD51D-related cancer predisposition, Li-fraumeni-like syndrome, breast cancer, familial, susceptibility to, 1, breast cancer, familial, susceptibility to, 2, breast cancer, familial, susceptibility to, 3, colorectal cancer, susceptibility to, 4, colorectal cancer, susceptibility to, on chromosome 15, ovarian cancer, familial, susceptibility to, 1, ovarian cancer, familial, susceptibility to, 2, ovarian cancer, familial, susceptibility to, 3, inherited hematologic cancer-predisposing syndrome, mosaic neurofibromatosis/schwannomatosis, tumor predisposition syndrome 2, prostate cancer, hereditary, X-linked 3, follicular lymphoma, susceptibility to, GPR161-related medulloblastoma predisposition, SAMD9L-related spectrum and myeloid neoplasm risk, HAVCR2-related cancer predisposition, EGLN1-related erythrocytosis and pheochromocytoma/paraganglioma predisposition

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

112 retrieved; paginated sample, class counts are floors:

42 conflicting classifications of pathogenicity, 37 uncertain significance, 10 pathogenic, 9 pathogenic/likely pathogenic, 9 benign/likely benign, 3 likely pathogenic, 1 benign, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
127720	NM_000465.4(BARD1):c.1690C>T (p.Gln564Ter)	BARD1	Pathogenic	criteria provided, multiple submitters, no conflicts
127725	NM_000465.4(BARD1):c.1935_1954dup (p.Glu652fs)	BARD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1400811	NM_000465.4(BARD1):c.316C>T (p.Gln106Ter)	BARD1	Pathogenic	criteria provided, multiple submitters, no conflicts
141702	NM_000465.4(BARD1):c.1921C>T (p.Arg641Ter)	BARD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
142734	NM_000465.4(BARD1):c.1212C>G (p.Tyr404Ter)	BARD1	Pathogenic	criteria provided, multiple submitters, no conflicts
1728915	NM_000465.4(BARD1):c.1133_1135delinsCC (p.Arg378fs)	BARD1	Pathogenic	criteria provided, multiple submitters, no conflicts
182036	NM_000465.4(BARD1):c.448C>T (p.Arg150Ter)	BARD1	Pathogenic	criteria provided, multiple submitters, no conflicts
185079	NM_000465.4(BARD1):c.298C>T (p.Gln100Ter)	BARD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
185366	NM_000465.4(BARD1):c.2268G>A (p.Trp756Ter)	BARD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
185846	NM_000465.4(BARD1):c.496C>T (p.Gln166Ter)	BARD1	Pathogenic	criteria provided, multiple submitters, no conflicts
186576	NM_000465.4(BARD1):c.539_540del (p.Ser179_Tyr180insTer)	BARD1	Pathogenic	criteria provided, multiple submitters, no conflicts
219726	NM_000465.4(BARD1):c.627_628del (p.Lys209fs)	BARD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
230523	NM_000465.4(BARD1):c.2300_2301del (p.Val767fs)	BARD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
231232	NM_000465.4(BARD1):c.69_70delinsTCCGGGAACGAGCCTCGTTCCGCGT (p.Ala25fs)	BARD1	Pathogenic	criteria provided, multiple submitters, no conflicts
233594	NM_000465.4(BARD1):c.55G>T (p.Glu19Ter)	BARD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4056225	NM_000465.4(BARD1):c.1436T>G (p.Leu479Ter)	BARD1	Pathogenic	criteria provided, single submitter
4056228	NM_000465.4(BARD1):c.1135A>T (p.Lys379Ter)	BARD1	Pathogenic	criteria provided, single submitter
479152	NM_000465.4(BARD1):c.1314+1G>A	BARD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
479187	NM_000465.4(BARD1):c.1905G>A (p.Trp635Ter)	BARD1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1066134	NM_000465.4(BARD1):c.2101C>T (p.Gln701Ter)	BARD1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
4056167	NM_000465.4(BARD1):c.2266del (p.Trp756fs)	BARD1	Likely pathogenic	criteria provided, single submitter
530167	NM_000465.4(BARD1):c.2001+1G>A	BARD1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
127713	NM_000465.4(BARD1):c.1217G>A (p.Arg406Gln)	BARD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
127716	NM_000465.4(BARD1):c.1568T>C (p.Val523Ala)	BARD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
127718	NM_000465.4(BARD1):c.1677+5G>A	BARD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
127722	NM_000465.4(BARD1):c.1718T>C (p.Ile573Thr)	BARD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
127730	NM_000465.4(BARD1):c.2116A>G (p.Lys706Glu)	BARD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
127743	NM_000465.4(BARD1):c.668A>G (p.Glu223Gly)	BARD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
127745	NM_000465.4(BARD1):c.709C>G (p.Gln237Glu)	BARD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
127747	NM_000465.4(BARD1):c.776A>G (p.Asp259Gly)	BARD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
BARD1	Act	PRAD	CIViC #549

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
BARD1	Definitive	Autosomal dominant	BARD1-related cancer predisposition	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BARD1	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BARD1	HGNC:952	ENSG00000138376	Q99728	BRCA1-associated RING domain protein 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BARD1	BRCA1-associated RING domain protein 1	E3 ubiquitin-protein ligase.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BARD1	Transcription factor	no	2.3.2.27	BRCT_dom, Znf_RING, Ankyrin_rpt

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
oocyte	1
secondary oocyte	1
tongue squamous epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BARD1	271	ubiquitous	marker	secondary oocyte, oocyte, tongue squamous epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BARD1	4,230

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BARD1	Q99728	11

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 42. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective DNA double strand break response due to BRCA1 loss of function	1	5710.0×	0.004	BARD1
Defective DNA double strand break response due to BARD1 loss of function	1	5710.0×	0.004	BARD1
Defective homologous recombination repair (HRR) due to PALB2 loss of function	1	951.7×	0.007	BARD1
Diseases of DNA Double-Strand Break Repair	1	815.7×	0.007	BARD1
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	1	815.7×	0.007	BARD1
Resolution of D-Loop Structures	1	634.4×	0.007	BARD1
Diseases of DNA repair	1	571.0×	0.007	BARD1
DNA Double Strand Break Response	1	475.8×	0.007	BARD1
Impaired BRCA2 binding to PALB2	1	456.8×	0.007	BARD1
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	1	423.0×	0.007	BARD1
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	1	423.0×	0.007	BARD1
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	1	423.0×	0.007	BARD1
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	1	393.8×	0.007	BARD1
Homologous DNA Pairing and Strand Exchange	1	380.7×	0.007	BARD1
Homology Directed Repair	1	308.6×	0.007	BARD1
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	1	308.6×	0.007	BARD1
Impaired BRCA2 binding to RAD51	1	308.6×	0.007	BARD1
Metalloprotease DUBs	1	300.5×	0.007	BARD1
Resolution of D-loop Structures through Holliday Junction Intermediates	1	300.5×	0.007	BARD1
HDR through Single Strand Annealing (SSA)	1	292.8×	0.007	BARD1
Presynaptic phase of homologous DNA pairing and strand exchange	1	271.9×	0.007	BARD1
DNA Double-Strand Break Repair	1	248.3×	0.008	BARD1
HDR through Homologous Recombination (HRR)	1	190.3×	0.010	BARD1
Nonhomologous End-Joining (NHEJ)	1	167.9×	0.010	BARD1
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks	1	146.4×	0.011	BARD1
G2/M Checkpoints	1	134.3×	0.011	BARD1
Regulation of TP53 Activity	1	132.8×	0.011	BARD1
Deubiquitination	1	124.1×	0.011	BARD1
UCH proteinases	1	124.1×	0.011	BARD1
G2/M DNA damage checkpoint	1	120.2×	0.011	BARD1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of mRNA 3’-end processing	1	16852.0×	0.001	BARD1
regulation of phosphorylation	1	2808.7×	0.002	BARD1
negative regulation of protein export from nucleus	1	2106.5×	0.002	BARD1
DNA strand resection involved in replication fork processing	1	2106.5×	0.002	BARD1
homologous recombination	1	1404.3×	0.003	BARD1
regulation of DNA damage checkpoint	1	1123.5×	0.003	BARD1
protein K6-linked ubiquitination	1	991.3×	0.003	BARD1
mitotic G2/M transition checkpoint	1	802.5×	0.003	BARD1
tissue homeostasis	1	561.7×	0.004	BARD1
cellular response to ionizing radiation	1	411.0×	0.005	BARD1
negative regulation of cell cycle	1	290.6×	0.006	BARD1
regulation of DNA repair	1	276.3×	0.006	BARD1
positive regulation of protein catabolic process	1	203.0×	0.008	BARD1
regulation of cell cycle	1	74.6×	0.019	BARD1
chromatin remodeling	1	73.0×	0.019	BARD1
DNA repair	1	63.8×	0.021	BARD1
positive regulation of apoptotic process	1	56.7×	0.022	BARD1
DNA damage response	1	53.5×	0.022	BARD1
protein ubiquitination	1	41.4×	0.027	BARD1
negative regulation of apoptotic process	1	34.8×	0.030	BARD1
regulation of transcription by RNA polymerase II	1	11.7×	0.086	BARD1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BARD1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BARD1	2.3.2.27	RING-type E3 ubiquitin transferase

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Drug repurposing candidates

0 approved/phased drugs hit cohort targets but don’t yet appear in disease-level clinical trials. Target-inhibition rationale is strongest for cancer driver genes; a bioactivity hit is a screening signal, not a treatment claim.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	BARD1

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
BARD1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.