Fanconi Anemia via the BRIP1/FANCJ Gene
Summary and Pricing
Test Method
Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture ProbesTest Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
---|---|---|---|---|---|
4843 | BRIP1 | 81479 | 81479,81479 | $990 | Order Options and Pricing |
Pricing Comments
Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.
An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.
This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.
Turnaround Time
3 weeks on average for standard orders or 2 weeks on average for STAT orders.
Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.
Targeted Testing
For ordering sequencing of targeted known variants, go to our Targeted Variants page.
Clinical Features and Genetics
Clinical Features
Fanconi Anemia (FA) is an inherited anemia associated with bone marrow failure (aplastic anemia), however, the clinical features of FA can expand well beyond hematologic anomalies. FA is also characterized by a range of physical abnormalities, pancytopenia, and predisposition to certain cancers - particularly acute myelogenous leukemia (AML), gynecologic and GI tract cancers, and cancers of the head and neck (Auerbach. 2009. PubMed ID: 19622403). FA patients are up to 800 fold more susceptible to AML than the general population with a median age of onset of 13 years (Rosenberg et al. 2003. PubMed ID: 12393424). Physical abnormalities include radial ray defects (absent thumb or radius), skin pigmentation defects, short stature, microphthalmia, renal and urinary tract defects, genital defects (males in particular), gastrointestinal malformations (atresia), congenital heart disease, hearing and central nervous system defects, and general developmental delay (Tischkowitz and Hodgson. 2003. PubMed ID: 12525534; Dokal. 2000. PubMed ID: 11030042). About one-third of FA patients have no obvious physical abnormalities and are diagnosed only after a family member is diagnosed, or after developing hematologic anomalies such as thromobocytopenia, leukopenia, and anemia (Giampietro et al. 1997. PubMed ID: 8986277).
A hallmark of FA is hypersensitivity of chromosomes to inter cross-strand linkage (ICL) agents such as diepoxybutane (DEB) or mitomycin C (MMC) (Sasaki and Tonomura. 1973. PubMed ID: 4352739). Exposure of primary cell cultures from FA patients to DEB or MMC results in chromosomal aberrations (breaks, radials, rearrangements) due to deficient DNA repair mechanisms that require functional products of the Fanconi anemia genes. For example, the FANCA, -B, -C, -E, -F, -G, -L, and -M proteins are part of a nuclear core complex that regulates monoubiquitination of the FANCD2 and FANCI proteins (ID complex) during S-phase and after exposure to DNA crosslinking agents (Moldovan and D'Andrea. 2009. PubMed ID: 19686080). In unaffected individuals, ubiquitination helps localize the ID complex to sites of DNA damage and facilitate repair, but in FA patients, this mechanism is impaired (Grompe and van de Vrugt. 2007. PubMed ID: 17488615; Smogorzewska et al. 2007. PubMed ID: 17412408).
Genetics
FA is a genetically heterogeneous disorder. To date, 22 FA or FA-like genes have been discovered. Inheritance is primarily autosomal recessive or X-linked, however a case of heterozygous FA-like syndrome was associated with a dominant-negative variant in the RAD51 (FANCR) gene (Ameziane et al. 2015. PubMed ID: 26681308). Approximately 86% of all cases are attributed to variants in three genes: FANCA (~ 60%), FANCC (~ 16%), and FANCG (~ 10%) (Auerbach. 2009. PubMed ID: 19622403). Since variants in FANCA are the most common cause of FA, it is important to note that large deletions make up over one-third of all reported pathogenic variants in FANCA. In the United States, the carrier frequency for Fanconi anemia is estimated at 1 in 181, and the incidence rate is estimated at 1 in 131,000 (http://www.fanconi.org/; Rosenberg et al. 2011. PubMed ID: 21739583). Nearly 95% of all FA cases are attributed to variants in eight genes, FANCA, -C, -G, -D1 (aka BRCA2), -D2, -E, -F, and –L that are either part of the core complex required for ID complex ubiquitination and facilitation of DNA repair or function directly in ICL recognition and repair (Grompe and van de Vrugt. 2007. PubMed ID: 17488615). FA is phenotypically diverse even among related patients that harbor the same variants; null alleles however are reported to result in more severe phenotypes (Faivre et al. 2000. PubMed ID: 11110674). FA affects males and females roughly equally and affects all ethnic groups.
Heterozygous variants in BRIP1/FANCJ are most commonly associated with an increased risk for developing breast and ovarian cancer (Seal et al. 2006. PubMed ID: 17033622; Rafnar et al. 2011. PubMed ID: 21964575), whereas biallelic variants in BRIP1/FANCJ are associated with FA (Levitus et al. 2005. PubMed ID: 16116423; Levran. 2005. PubMed ID: 16116424). The BRIP1/FANCJ protein interacts directly with BRCA1 protein and functions in part as a helicase important for unwinding DNA during cross-link repair (Cantor et al. 2001. PubMed ID: 11301010; Cantor et al. 2004. PubMed ID: 14983014). Though many variants in BRIP1/FANCJ have been reported to be associated with breast and ovarian cancer risk, fewer variants have been reported to be associated with FA which include a recurrent nonsense variant (p.Arg798*), and several splice and missense variants (Chandrasekharappa et al. 2013. PubMed ID: 23613520; Levitus et al. 2005. PubMed ID: 16116423; Levran. 2005. PubMed ID: 16116424). Several large deletions have been reported for the BRIP1/FANCJ gene and all were reported in association with breast and ovarian cancer risk (Tung et al. 2015. PubMed ID: 25186627; Norquist et al. 2016. PubMed ID: 26720728). Variants in FANCJ are an infrequent cause of FA and account for account for < 1% of all FA cases (Shimamura and Alter. 2010. PubMed ID: 20417588).
Clinical Sensitivity - Sequencing with CNV PG-Select
Pathogenic variants in the BRIP1/FANCJ gene account for <1% of all Fanconi anemia (FA) cases (Auerbach. 2009. PubMed ID: 19622403; Shimamura and Alter. 2010. PubMed ID: 20417588).
Several multi-exon deletions have been reported for the BRIP1/FANCJ gene, however, they have all been reported in association with incrased risk for breast and ovararian cancer and not in patients with FA (The Rockefeller University Fanconi Anemia Mutation Database; Human Gene Mutation Database).
Testing Strategy
This test provides full coverage of all coding exons of the BRIP1/FANCJ gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.
Indications for Test
Candidates are patients with clinical features of FA, individuals with a family history of FA, patients with early onset hematologic malignancies or solid tumors, and patients who develop aplastic anemia and hematologic disorders at any age even if they present no other physical abnormalities. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in BRIP1.
Candidates are patients with clinical features of FA, individuals with a family history of FA, patients with early onset hematologic malignancies or solid tumors, and patients who develop aplastic anemia and hematologic disorders at any age even if they present no other physical abnormalities. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in BRIP1.
Gene
Official Gene Symbol | OMIM ID |
---|---|
BRIP1 | 605882 |
Inheritance | Abbreviation |
---|---|
Autosomal Dominant | AD |
Autosomal Recessive | AR |
X-Linked | XL |
Mitochondrial | MT |
Disease
Name | Inheritance | OMIM ID |
---|---|---|
Fanconi Anemia, Complementation Group J | AR | 609054 |
Related Tests
Citations
- Ameziane et al. 2015. PubMed ID: 26681308
- Auerbach. 2009. PubMed ID: 19622403
- Cantor et al. 2001. PubMed ID: 11301010
- Cantor et al. 2004. PubMed ID: 14983014
- Chandrasekharappa et al. 2013. PubMed ID: 23613520
- Dokal. 2000. PubMed ID: 11030042
- Faivre et al. 2000. PubMed ID: 11110674
- Fanconi Anemia Research Fund, Inc.
- Giampietro et al. 1997. PubMed ID: 8986277
- Grompe and van de Vrught. 2007. PubMed ID: 17488615
- Human Gene Mutation Database (Bio-base).
- Levitus et al. 2005. PubMed ID: 16116423
- Levran et al. 2005. PubMed ID: 16116424
- Moldovan and D’Andrea. 2009. PubMed ID: 19686080
- Norquist et al. 2016. PubMed ID: 26720728
- Rafnar et al. 2011. PubMed ID: 21964575
- Rosenberg et al. 2003. PubMed ID: 12393424
- Rosenberg et al. 2011. PubMed ID: 21739583
- Sasaki and Tonomura. 1973. PubMed ID: 4352739
- Seal et al. 2006. PubMed ID: 17033622
- Shimamura and Alter. 2010 PubMed ID: 20417588
- Smogorzewska et al. 2007. PubMed ID: 17412408
- The Rockefeller University Fanconi Anemia Mutation Database.
- Tischkowitz and Hodgson. 2003. PubMed ID: 12525534
- Tung et al. 2015. PubMed ID: 25186627
Ordering/Specimens
Ordering Options
We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.
myPrevent - Online Ordering
- The test can be added to your online orders in the Summary and Pricing section.
- Once the test has been added log in to myPrevent to fill out an online requisition form.
- PGnome sequencing panels can be ordered via the myPrevent portal only at this time.
Requisition Form
- A completed requisition form must accompany all specimens.
- Billing information along with specimen and shipping instructions are within the requisition form.
- All testing must be ordered by a qualified healthcare provider.
For Requisition Forms, visit our Forms page
If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.
Specimen Types
ORDER OPTIONS
View Ordering Instructions1) Select Test Type
2) Select Additional Test Options
No Additional Test Options are available for this test.