Panel Description
The Beacon Expanded + Opt-In carrier screening is the largest pan-ethnic screening panel available. This panel analyzes genes for pathogenic mutations known to cause autosomal recessive and X-linked disorders. All genes from the Beacon Expanded Carrier Screening panel are included with the addition of 9 “opt-in” genes that are associated with mild or adult-onset presentation of disease, but may be of interest to specific families or clinics.
Diseases targeted: >400 Autosomal Recessive and X-linked Inherited Disorders
Our technology establishes Beacon as the most intensive carrier screening with the highest accuracy available.
- Sequence variants and small insertions/deletions: unless otherwise specified, whole gene sequencing (coding regions and adjacent intronic/splice regions) is performed with >99% of bases covered by at least 20 independent sequence reads (“20x”). Additionally, intronic and promoter mutations specified in ClinVar and the Human Gene Mutation Database (HGMD) are targeted with >98% sensitivity.
- Deletion/duplications (del/dup): copy number variants (also known as deletions/duplications, or del/dup for short) are detected using Fulgent’s sophisticated bioinformatic algorithm, CNVexonTM. Pathogenic variants found by this method are confirmed by Sanger sequencing, MLPA, or quantitative PCR (qPCR).
- Fragile X: The trinucleotide repeat (CGG) expansion in the 5’ untranslated region of FMR1 is detected by repeat-primed PCR (rpPCR). Premutation carriers are sequenced by Sanger sequencing to detect AGG interruptions.
- Spinal Muscular Atrophy: copy number changes in the SMN1 gene is screened by NGS and confirmed by MLPA. Point mutations for spinal muscular atrophy are not detected due to high sequence homology.
- Pseudogenes: proprietary bioinformatics tools are employed to identify carrier mutations in disease genes (such as GBA for Gaucher disease and HBA1/HBA2 for alpha thalassemia) which have highly similar inactive counterparts.
Reporting options: Only variants classified as “Pathogenic” or “Likely Pathogenic” using the ACMG guidelines for sequence variant interpretation will be reported.
Detection rate: A broad range of laboratory and computational tools are employed to ensure the highest detection rate. The analytical detection rate for all genes is >98%.
*Male patients will not be screened for X-linked conditions (e.g., FMR1, etc.). If an X-linked condition is suspected in a male patient, please contact Fulgent Genetics or a genetics professional about diagnostic testing for that particular disorder.
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Gene Specifics:
Gene | Notes |
---|---|
ARX | Heterozygous polyalanine expansions of >7 repeats (21bp) in the ARX gene in females may not be detected by this method. |
CD40LG | The current testing method does not assess trinucleotide repeat expansions in this gene. |
CRYL1 | As mutations in the CRYL1 gene are not known to be associated with any clinical condition, sequence variants in this gene are not analyzed. However, to increase copy number detection sensitivity for large deletions including this gene and a neighboring on gene on the panel (GJB6, also known as connexin 30), this gene is evaluated for copy number variation. |
SMN1 | The current testing method detects sequencing variants in exon 7 and copy number variations in exons 7-8 of the SMN1 gene (NM_022874.2). Sequencing and deletion/duplication analysis are not performed on any other region in this gene. About 5%-8% of the population have two copies of SMN1 on a single chromosome and a deletion on the other chromosome, known as a [2+0] configuration (PubMed: 20301526). The current testing method cannot directly detect carriers with a [2+0] SMN1 configuration, but can detect linkage between the silent carrier allele and certain population-specific single nucleotide changes. As a result, a negative result for carrier testing greatly reduces but does not eliminate the chance that a person is a carrier. The 3-copy SMN1 state can be detected by this test and will be reported out if present. |
Resources
- Carrier screening for genetic conditions. Committee Opinion No. 691. American College of Obstetricians and Gynecologists. Obstet Gynecol 2017;129:e41-55
- Carrier screening in the age of genomic medicine. Committee Opinion No. 690. American College of Obstetricians and Gynecologists. Obstet Gynecol 2017;129e35-40
- Edwards et al. Expanded Carrier Screening in Reproductive Medicine–Points to Consider. A Joint Statement of the American College of Medical Genetics and Genomics, American College of Obstetricians and Gynecologists, National Society of Genetic Counselors, Perinatal Quality Foundation, and Society for Maternal-Fetal Medicine. Obstet Gynecol 2015; 125(3)
- Prior TW. Carrier screening for spinal muscular atrophy. ACMG Practice Guidelines. Genet Med 2008:10(11):840-842
- Sherman S et al. Fragile X syndrome: Diagnostic and carrier testing. ACMG Practice Guidelines. Genet Med 2005:7(8):584-587
- Watson MS et al. Cystic fibrosis population carrier screening: 2004 revision of American College of Medical Genetics mutation panel. ACMG Policy Statement. Genet Med 2004:6(5):387-391