Breast-ovarian cancer, familial, susceptibility to, 1: genes and variants
Explore variant evidence for Breast-ovarian cancer, familial, susceptibility to, 1 across 10 analyzed proteins (RAD51C, PALB2, MSH2, ATP7B, STK11 and 5 more). Linked ClinVar records include 14 pathogenic or likely pathogenic variants, 671 variants of uncertain significance and 213 with conflicting classifications.
Coverage includes proteins already analyzed in CATVariant, not every gene involved in this condition. Database links are associations, not an assessment of clinical gene–disease validity. Computable evidence prioritizes variants for expert review and does not reclassify them. Source labels are pooled across this disease family.
Data updated 2026-10-10. Automated aggregation, not a clinical review date.
Download variant evidence (CSV)
Genes linked to Breast-ovarian cancer, familial, susceptibility to, 1
RAD51C: DNA repair protein RAD51 homolog 3
It participates in RAD51-paralog complexes that promote homologous-recombination repair and restart damaged replication forks. Heterozygous loss-of-function variants increase ovarian and breast-cancer risk, while biallelic variants can cause Fanconi anemia.
9 ClinVar pathogenic / likely pathogenic and 198 uncertain variants in RAD51C have source records linked to Breast-ovarian cancer, familial, susceptibility to, 1. Association strength is not clinical gene validity.
PALB2: Partner and localizer of BRCA2
It physically links BRCA1 and BRCA2 and helps recruit BRCA2-RAD51 repair machinery to DNA double-strand breaks. Heterozygous loss-of-function variants substantially increase breast and pancreatic cancer risk, while biallelic variants cause Fanconi anemia subtype N.
1 ClinVar pathogenic / likely pathogenic and 79 uncertain variants in PALB2 have source records linked to Breast-ovarian cancer, familial, susceptibility to, 1. Association strength is not clinical gene validity.
MSH2: DNA mismatch repair protein Msh2
The protein forms mismatch-recognition complexes with MSH6 or MSH3 that detect base mismatches and insertion-deletion loops in DNA. This first step of mismatch repair helps preserve genome integrity, and inherited MSH2 variants are associated with Lynch syndrome.
1 ClinVar pathogenic / likely pathogenic and 1 uncertain variants in MSH2 have source records linked to Breast-ovarian cancer, familial, susceptibility to, 1. Association strength is not clinical gene validity.
ATP7B: Copper-transporting ATPase 2
A copper-transporting ATPase that moves excess copper out of cells and helps deliver it from liver cells into bile. Its trafficking between intracellular membranes is central to copper homeostasis, and ATP7B dysfunction causes Wilson disease.
1 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in ATP7B have source records linked to Breast-ovarian cancer, familial, susceptibility to, 1. Association strength is not clinical gene validity.
STK11: Serine/threonine-protein kinase STK11
It activates AMPK-family kinases to coordinate cellular energy sensing, polarity, and growth restraint. Germline loss-of-function variants cause Peutz-Jeghers syndrome and its associated cancer predisposition, while somatic loss is common in lung and other cancers.
1 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in STK11 have source records linked to Breast-ovarian cancer, familial, susceptibility to, 1. Association strength is not clinical gene validity.
TP53: Cellular tumor antigen p53
It coordinates transcriptional responses to DNA damage and other cellular stresses, promoting cell-cycle arrest, senescence, DNA repair, or apoptosis when appropriate. Loss of this tumor-suppressive control is one of the most common events in cancer, while germline pathogenic variants cause Li-Fraumeni syndrome.
1 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in TP53 have source records linked to Breast-ovarian cancer, familial, susceptibility to, 1. Association strength is not clinical gene validity.
BRIP1: Fanconi anemia group J protein
It unwinds DNA structures and works with BRCA1 and the Fanconi-anemia pathway to repair damaged replication intermediates and interstrand crosslinks. Biallelic loss causes Fanconi anemia group J, while heterozygous loss-of-function variants increase ovarian-cancer risk.
0 ClinVar pathogenic / likely pathogenic and 3 uncertain variants in BRIP1 have source records linked to Breast-ovarian cancer, familial, susceptibility to, 1. Association strength is not clinical gene validity.
BRCA2: Breast cancer type 2 susceptibility protein
It loads RAD51 onto damaged DNA to enable homologous recombination and also protects stressed replication forks from degradation. Germline loss-of-function variants strongly predispose to breast, ovarian, prostate, pancreatic, and other cancers.
0 ClinVar pathogenic / likely pathogenic and 1 uncertain variants in BRCA2 have source records linked to Breast-ovarian cancer, familial, susceptibility to, 1. Association strength is not clinical gene validity.
BRCA1: Breast cancer type 1 susceptibility protein
It coordinates DNA-damage signaling and homologous-recombination repair while helping protect stalled replication forks and chromosome integrity. Germline loss-of-function variants strongly predispose to breast and ovarian cancer and increase risk for several other malignancies.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in BRCA1 have source records linked to Breast-ovarian cancer, familial, susceptibility to, 1. Association strength is not clinical gene validity.
RAD51D: DNA repair protein RAD51 homolog 4
It supports RAD51-mediated homologous recombination and chromosome stability after DNA double-strand breaks. Heterozygous loss-of-function variants confer substantial ovarian-cancer risk and a more moderate increase in breast-cancer susceptibility.
0 ClinVar pathogenic / likely pathogenic and 595 uncertain variants in RAD51D have source records linked to Breast-ovarian cancer, familial, susceptibility to, 1. Association strength is not clinical gene validity.
Weakly linked (only a few uncertain records): RAD50, CHEK2, MLH1, MSH6 and NBN.
Where Breast-ovarian cancer, familial, susceptibility to, 1 variants cluster
- RAD51C Interaction with RAD51B, RAD51D and XRCC3 (positions 79–136): 6 of 9 ClinVar pathogenic / likely pathogenic variants, 4.3× more than its size predicts.
ClinVar pathogenic and likely pathogenic variants linked to Breast-ovarian cancer, familial, susceptibility to, 1
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| RAD51C T132P | 132 | Interaction with RAD51B, RAD51D and XRCC3 | Pathogenic / likely pathogenic (★★) |
| RAD51C C135F | 135 | Interaction with RAD51B, RAD51D and XRCC3 | Pathogenic / likely pathogenic (★★) |
| ATP7B L795F | 795 | Cytoplasmic | Pathogenic / likely pathogenic (★★) |
| RAD51C G114E | 114 | Interaction with RAD51B, RAD51D and XRCC3 | Pathogenic / likely pathogenic (★★) |
| RAD51C G125V | 125 | Interaction with RAD51B, RAD51D and XRCC3 | Pathogenic / likely pathogenic (★★) |
| MSH2 N671I | 671 | Interaction with EXO1 | Pathogenic / likely pathogenic (★★) |
| PALB2 M1I | 1 | Required for its oligomerization and is importan | Pathogenic / likely pathogenic (★★) |
| RAD51C L138F | 138 | Pathogenic / likely pathogenic (★★) | |
| RAD51C T121R | 121 | Interaction with RAD51B, RAD51D and XRCC3 | Pathogenic / likely pathogenic (★) |
| RAD51C K131E | 131 | Interaction with RAD51B, RAD51D and XRCC3 | Pathogenic / likely pathogenic (★) |
| RAD51C G150V | 150 | Pathogenic / likely pathogenic (★) | |
| RAD51C R312P | 312 | Pathogenic / likely pathogenic (★) | |
| STK11 K41E | 41 | Pathogenic / likely pathogenic (★) | |
| TP53 N131H | 131 | DNA binding | Pathogenic / likely pathogenic (★) |
Uncertain variants prioritized for review in Breast-ovarian cancer, familial, susceptibility to, 1
| Variant | Position | Protein part | Clinical label | Evidence |
|---|---|---|---|---|
| RAD51C K131I | 131 | Interaction with RAD51B, RAD51D and XRCC3 | Conflicting reports (★) | +7: 2 other pathogenic changes within 3 positions; K131E at the same position is pathogenic; seen in 6.9e-07 of gnomAD DNA copies; REVEL 0.956 |
| RAD51C G125S | 125 | Interaction with RAD51B, RAD51D and XRCC3 | Uncertain (★★) | +7: G125V at the same position is pathogenic; seen in 6.9e-07 of gnomAD DNA copies; REVEL 0.956 |
| RAD51C K131Q | 131 | Interaction with RAD51B, RAD51D and XRCC3 | Conflicting reports (★) | +6: 2 other pathogenic changes within 3 positions; K131E at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 0.96 |
| RAD51C C135W | 135 | Interaction with RAD51B, RAD51D and XRCC3 | Conflicting reports (★) | +6: 3 other pathogenic changes within 3 positions; C135F at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 0.92 |
Which prediction tools work for Breast-ovarian cancer, familial, susceptibility to, 1
Observed separation of ClinVar pathogenic / likely pathogenic from benign / likely benign variants (AUROC × 100). This benchmark is not a clinical recommendation.
- PolyPhen-2: 93 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- SIFT: 84 out of 100
- CATVariant: 74 out of 100 (learned from overlapping clinical labels, so this is optimistic)
Same protein, different disease
- Lynch syndrome also has ClinVar records linked to MSH2 variants; they fall mostly in different places as the Breast-ovarian cancer, familial, susceptibility to, 1 variants (22 pathogenic / likely pathogenic).
- Hereditary nonpolyposis colorectal neoplasms also has ClinVar records linked to MSH2 variants; they fall mostly in different places as the Breast-ovarian cancer, familial, susceptibility to, 1 variants (12 pathogenic / likely pathogenic).
- Li-Fraumeni syndrome also has ClinVar records linked to TP53 variants; they fall mostly in different places as the Breast-ovarian cancer, familial, susceptibility to, 1 variants (188 pathogenic / likely pathogenic).
- Adrenocortical carcinoma, hereditary also has ClinVar records linked to TP53 variants; they fall mostly in different places as the Breast-ovarian cancer, familial, susceptibility to, 1 variants (23 pathogenic / likely pathogenic).
- Acute myeloid leukemia also has ClinVar records linked to TP53 variants; they fall mostly in different places as the Breast-ovarian cancer, familial, susceptibility to, 1 variants (6 pathogenic / likely pathogenic).
- Hereditary breast cancer also has ClinVar records linked to TP53 variants; they fall mostly in different places as the Breast-ovarian cancer, familial, susceptibility to, 1 variants (5 pathogenic / likely pathogenic).
- Glioma susceptibility 1 also has ClinVar records linked to TP53 variants; they fall mostly in different places as the Breast-ovarian cancer, familial, susceptibility to, 1 variants (5 pathogenic / likely pathogenic).
- Wilson disease also has ClinVar records linked to ATP7B variants; they fall mostly in different places as the Breast-ovarian cancer, familial, susceptibility to, 1 variants (222 pathogenic / likely pathogenic).
- Peutz-Jeghers syndrome also has ClinVar records linked to STK11 variants; they fall mostly in different places as the Breast-ovarian cancer, familial, susceptibility to, 1 variants (24 pathogenic / likely pathogenic).
- Melanoma, cutaneous malignant, susceptibility to, 8 also has ClinVar records linked to STK11 variants; they fall mostly in different places as the Breast-ovarian cancer, familial, susceptibility to, 1 variants (4 pathogenic / likely pathogenic).
Diseases related to Breast-ovarian cancer, familial, susceptibility to, 1
- Hereditary breast ovarian cancer syndrome, also linked to BRCA1, BRCA2, BRIP1, PALB2 and 3 more
- Ovarian cancer, also linked to BRCA1, BRCA2, BRIP1, MSH2 and 2 more
- Breast and/or ovarian cancer, also linked to BRIP1, MSH2, RAD51C, RAD51D and 2 more
- Fanconi anemia complementation group J, also linked to BRCA1, BRCA2, BRIP1, PALB2 and 1 more
- Hereditary breast cancer, also linked to BRCA1, BRCA2, BRIP1, PALB2 and 1 more
- Gastric cancer, also linked to BRIP1, PALB2, RAD51C, RAD51D and 1 more
- Familial pancreatic carcinoma, also linked to BRCA1, BRCA2, PALB2, STK11 and 1 more
- Fanconi anemia, also linked to BRCA2, BRIP1, PALB2 and RAD51C
- Ovarian neoplasm, also linked to BRCA1, BRCA2, BRIP1 and TP53
- Familial ovarian cancer, also linked to BRIP1, RAD51C and RAD51D
- Acute myeloid leukemia, also linked to PALB2 and TP53
- Colorectal cancer, also linked to MSH2 and TP53
Frequently asked questions
Which genes have records linked to Breast-ovarian cancer, familial, susceptibility to, 1?
This view contains 10 analyzed proteins: RAD51C, PALB2, MSH2, ATP7B, STK11 and 5 more. Links come from clinical records and association databases. They do not imply that every listed gene is a validated cause, and missing genes may not yet be analyzed.
What do the clinical classifications mean?
Linked records include 14 pathogenic or likely pathogenic variants, 671 variants of uncertain significance and 213 with conflicting classifications. Labels summarize source records; multi-condition records may not make a separate assertion for this disease. Check the original record and review status.
Does the evidence score change a VUS classification?
No. 4 VUS or conflicting variants reach the likely-pathogenic points range on the computable criteria available here. This is a research prioritization signal, not a clinical classification. Patient, family and other required evidence may be missing.
Can I download the variant evidence?
Download the CSV for all 904 variants in the selected disease scope, including clinical labels, review status, evidence criteria, predictor scores, functional measurements and population frequency where available.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from eligible public CATVariant analyses of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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