PALB2 Gene Sequence and Deletion/Duplication

PALB2 is a tumor suppressor gene associated with breast and pancreatic cancer susceptibility.  


PALB2 is a tumor suppressor gene associated with breast and pancreatic cancer susceptibility.  

Disease Name 
Fanconi anemia
Breast cancer
Pancreatic cancer
Disease Information 

Individuals who have one PALB2 mutation have increased lifetime risks to develop breast, pancreatic, ovarian and possibly other cancers. Cancer risks associated with having one PALB2 mutation follow an autosomal dominant inheritance pattern. 

Females with a PALB2 mutation have a 2- to 4-fold increased risk for breast cancer.1,2 A 2014 article concluded that in the context of a strong family history, mutations in PALB2 may be associated with up to a 58% risk of female breast cancer. Without a family history, the risk for female breast cancer was estimated to be 33% (the difference attributed to genetic and/or environmental modifiers).3 Studies have identified PALB2 mutations in 1-3% of families with pancreatic cancer; however, the exact lifetime pancreatic cancer risk has not yet been established.4,5 Additionally, further studies have shown an increased risk for ovarian cancer.6,7

Individuals with two PALB2 mutations can have a subgroup of Fanconi anemia called complementation group N (FA-N), which follows an autosomal recessive inheritance pattern. Fanconi anemia is characterized by physical abnormalities including short stature, abnormal skin pigmentation, malformations of the skeletal and central nervous system, developmental delays, and bone marrow failure. Individuals with two PALB2 mutations are considered to be at an increased risk for several types of childhood cancers, including medulloblastoma, neuroblastoma, and Wilms tumor.8

The PALB2 gene is involved in the Fanconi anemia (FA)–BRCA pathway, which is critical for DNA repair; it interacts with BRCA2 to stabilize the protein. 

Testing Benefits & Indication 

Genetic testing is useful to:

  • Diagnose a personal and/or family history suggestive of hereditary breast and/or pancreatic cancer  
  • Provide appropriate screening recommendations and risk-reducing options for PALB2 mutation-positive patients and their relatives
  • Confirm a suspected diagnosis of Fanconi anemia 

PALB2 genetic testing may be indicated for:

  • Any individual with a personal and/or family history suggestive of hereditary breast and/or pancreatic cancer
    • These individuals may have previously tested negative for BRCA1/2 mutations or may be considering BRCA genetic testing
  • Any individual with a confirmed or suspected diagnosis of Fanconi anemia
Test Description 

PALB2 coding exons 1-13 and well into the 5’ and 3’ ends of all the introns and untranslated regions are analyzed by sequencing. Gross deletion/duplication analysis determines gene copy number for coding exons 1-13. Clinically significant intronic findings beyond 5 base pairs are always reported. Intronic variants of unknown or unlikely clinical significance are not reported beyond 5 base pairs from the splice junction. Genomic deoxyribonucleic acid (gDNA) is isolated from the patient’s specimen using standardized methodology and quantified. Sequence enrichment of the targeted coding exons and adjacent intronic nucleotides is carried out by a bait- capture methodology, using long biotinylated oligonucleotide probes followed by polymerase chain reaction (PCR) and next generation sequencing (NGS). Sanger sequencing is performed for any regions missing or with insufficient read depth coverage for reliable heterozygous variant detection. Reportable small insertions and deletions, potentially homozygous variants, variants in regions complicated by pseudogene interference, and single nucleotide variant calls not satisfying 100x depth of coverage and 40% het ratio thresholds are verified by Sanger sequencing.9  Gross deletion/duplication analysis of PALB2 using read-depth from NGS data is also performed. Any copy number changes detected by NGS are confirmed by targeted chromosomal microarray and/or multiplex ligation-dependent probe amplification (MLPA).

Mutation Detection Rate 

Ambry's PALB2 analysis can detect >99.9% of described mutations in the gene, when present (analytic sensitivity).

Specimen Requirements 

Complete specimen requirements are available here or by downloading the PDF found above in the Quick Links section at the top of this page

Turnaround Time 
2366 PALB2 Gene Sequence and Deletion and Duplication Analysis 14-21
2362 PALB2 Specific Site Analysis 14-21


  1. Slater EP, et al. PALB2 mutations in European familial pancreatic cancer families. Clin Genet. 2010. 78(5):490-4.
  2. Casadei S, et al. Contribution of inherited mutations in the BRCA2-interacting protein PALB2 to familial breast cancer. Cancer Res. 2011. 71(6):2222-9.
  3. Antoniou AC, et al.  Breast-cancer risk in families with mutations in PALB2NEJM.  2014; 371(6):497-506.
  4. Tischkowitz M, et al. Analysis of PALB2/FANCN-associated breast cancer families. Proc Natl Acad Sci USA. 2007 Apr 17; 104(16):6788-93.
  5. Jones A, et al. Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene. Science. 2009; 324(5924):217. 
  6. Walsh T, et al. Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing. Proc Natl Acad Sci U S A. 2011. 108(44):18032-7.
  7. Norquist BM, et al. Inherited mutations in women with ovarian carcinoma. JAMA Oncol. 2015 Dec 30:1-9. [Epub ahead of print].
  8. Reid S, et al. Biallelic mutations in PALB2 cause Fanconi anemia subtype FA-N and predispose to childhood cancer. Nat Genet. 2007 Feb; 39(2):142-3. 
  9. Mu W, et al. Sanger confirmation is required to achieve optimal sensitivity and specificity in next-generation sequencing panel testing. J Mol Diagn. 2016. 18(6):923-932.