Cholestasis Panel

SEQmethod-seq-icon Our Sequence Analysis is based on a proprietary targeted sequencing method OS-Seq™ and offers panels targeted for genes associated with certain phenotypes. A standard way to analyze NGS data for finding the genetic cause for Mendelian disorders. Results in 21 days. DEL/DUPmethod-dup-icon Targeted Del/Dup (CNV) analysis is used to detect bigger disease causing deletions or duplications from the disease-associated genes. Results in 21 days. PLUSmethod-plus-icon Plus Analysis combines Sequence + Del/Dup (CNV) Analysis providing increased diagnostic yield in certain clinical conditions, where the underlying genetic defect may be detectable by either of the analysis methods. Results in 21 days.

Test code: GA0501

The Blueprint Genetics Cholestasis Panel is a 31 gene test for genetic diagnostics of patients with clinical suspicion of Alagille syndrome, citrullinemia type 2, Crigler-Najjar syndrome types 1 and 2, dubin-Johnson syndrome, Gilbert syndrome, intrahepatic cholestasis of pregnancy type 3 or progressive familial intrahepatic cholestasis types 1-4.

Large majority of the disease targeted by this panel are inherited in autosomal recessive manner but Alagille syndrome is inherited by autosomal dominant mutations (JAG1) and cholestasis is associated to both recessive and dominant ABCB4 mutations. The panel cover also relatively benign disorders causing laboratory findings mimicking cholestasis such as hyperbilirubinemia (Gilbert syndrome, UGT1A1) and benign cholestasis (Dubin-Johnson syndrome; ABCC2).

About Cholestasis

Cholestasis is characterized by jaundice and pruritus. It can present as the hallmark feature in progressive familial intrahepatic cholestasis (PFIC) or as a feature in other inherited disorders such as Alagille syndrome where cholestasis occur in 95% of cases in neonatal period. PFIC is a group of autosomal recessive liver disorders due to defects in bile secretion and is characterized by intrahepatic cholestasis with disease onset usually in infancy and childhood (PFIC types 1-4, caused ATP8B1, ABCB11, ABCB4 and TJP2). PFIC patients usually develop fibrosis and end-stage liver disease before adulthood. Defects in PFIC-associated genes ATP8B1 and ABCB11 may also cause a milder disease called benign recurrent intrahepatic cholestasis. There are several other inherited disorders where cholestasis is frequent such as Alagille syndrome (JAG1 and NOTCH2), arthrogryposis, renal dysfunction, and cholestasis syndrome (ARC syndrome; VPS33B and VIPAS39), alpha-1-antitrypsin deficiency (SERPINA1), citrullinemia (SLC25A13), congenital defects of bile acid synthesis (HSD3B7 and AKR1D1), familial hypercholanemia (TJP2 and BAAT) and neonatal ichthyosis-sclerosing cholangitis syndrome (CLDN1). Prevalence of PFIC is unknown, Dubin-Johnson 1:1,300 in Iranian or Moroccan Jews, Alagille syndrome 1:30,000, Crigler-Najjar syndrome 1:1,000,000, whereas the Gilbert syndrome prevalence is 3-7% in population but it does not cause clinical symptoms.


Results in 3-4 weeks. We do not offer a maternal cell contamination (MCC) test at the moment. We offer prenatal testing only for cases where the maternal cell contamination studies (MCC) are done by a local genetic laboratory. Read more.

Genes in the Cholestasis Panel and their clinical significance
GeneAssociated phenotypesInheritanceClinVarHGMD
ABCB4Gallbladder disease, Low phospholipid-associated cholelithiasis, CholestasisAD/AR16202
ABCC2Dubin-Johnson syndromeAD/AR1651
ATP8B1Intrahepatic cholestasis of pregnancy, Familial intrahepatic cholestasis, recurrent, Cholestasis, progressive familial intrahepaticAD/AR17120
CFTRCystic fibrosisAR3661767
CYP7B1Bile acid synthesis defectAR1341
DGUOKMitochondrial DNA depletion syndromeAR1960
EPCAMDiarrhea 5, with tufting enteropathy, congenital, Colorectal cancer, hereditary nonpolyposisAD/AR1563
JAG1Alagille syndromeAD102557
LCTLactase deficiencyAR1024
MKS1Bardet-Biedl syndrome, Meckel syndromeAR3947
MYO5B*Diarrhea, with microvillus atrophyAR955
NEUROG3Diarrhea, malabsorptive, congenitalAR29
NOTCH2*Alagille syndrome, Hajdu-Cheney syndromeAD2156
NPC1Niemann-Pick diseaseAR73441
NPC2Niemann-pick diseaseAR1627
NPHP1Nephronophthisis, Joubert syndrome, Senior-Loken syndromeAR1264
NPHP3Nephronophthisis, Renal-hepatic-pancreatic dysplasia, Meckel syndromeAR2071
NPHP4Nephronophthisis, Senior-Loken syndromeAR10104
SERPINA1Alpha-1-antitrypsin deficiencyAR2982
SLC25A13Citrin deficiencyAR20106
SLC26A3Diarrhea, secretory chloride, congenitalAR5571
SMPD1Niemann-Pick diseaseAR52230
SPINT2Diarrhea, secretory sodium, congenitalAD610
TJP2Cholestasis, progressive familial intrahepatic, Hypercholanemia, familialAR1515
TMEM216Joubert syndrome, Meckel syndromeAR88
TRMULiver failure, infantile, Reversible infantile respiratory chain deficiencyAR1216
TTC37Trichohepatoenteric syndromeAR1036
UGT1A1Crigler-Najjar syndrome, Gilbert syndromeAD/AR25140
VPS33BArthrogryposis - renal dysfunction - cholestasisAD/AR953
  • * Some regions of the gene are duplicated in the genome leading to limited sensitivity within the regions. Thus, low-quality variants are filtered out from the duplicated regions and only high-quality variants confirmed by other methods are reported out. Read more.

Gene, refers to HGNC approved gene symbol; Inheritance to inheritance patterns such as autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL); ClinVar, refers to a number of variants in the gene classified as pathogenic or likely pathogenic in ClinVar (; HGMD, refers to a number of variants with possible disease association in the gene listed in Human Gene Mutation Database (HGMD, The list of associated (gene specific) phenotypes are generated from CDG ( or Orphanet ( databases.

Blueprint Genetics offers a comprehensive cholestasis panel that covers classical genes associated with Alagille syndrome, arthrogryposis, renal dysfunction, and cholestasis 1, citrullinemia type 2, congenital bile acid synthesis defect type 3, Crigler-Najjar syndrome types 1 and 2, dubin-Johnson syndrome, emphysema, related to alpha-1-antitrypsin deficiency, Gilbert syndrome, intrahepatic cholestasis of pregnancy type 3, progressive familial intrahepatic cholestasis types 1-4, transient infantile liver failure and tyrosinemia type 1. The genes are carefully selected based on the existing scientific evidence, our experience and most current mutation databases. Candidate genes are excluded from this first-line diagnostic test. The test does not recognise balanced translocations or complex inversions, and it may not detect low-level mosaicism. The test should not be used for analysis of sequence repeats or for diagnosis of disorders caused by mutations in the mitochondrial DNA.

Please see our latest validation report showing sensitivity and specificity for SNPs and indels, sequencing depth, % of the nucleotides reached at least 15x coverage etc. If the Panel is not present in the report, data will be published when the Panel becomes available for ordering. Analytical validation is a continuous process at Blueprint Genetics. Our mission is to improve the quality of the sequencing process and each modification is followed by our standardized validation process. All the Panels available for ordering have sensitivity and specificity higher than > 0.99 to detect single nucleotide polymorphisms and a high sensitivity for indels ranging 1-19 bp. The diagnostic yield varies substantially depending on the used assay, referring healthcare professional, hospital and country. Blueprint Genetics’ Plus Analysis (Seq+Del/Dup) maximizes the chance to find molecular genetic diagnosis for your patient although Sequence Analysis or Del/Dup Analysis may be cost-effective first line test if your patient’s phenotype is suggestive for a specific mutation profile. Detection limit for Del/Dup analysis varies through the genome from one to six exon Del/Dups depending on exon size, sequencing coverage and sequence content.

The sequencing data generated in our laboratory is analyzed with our proprietary data analysis and annotation pipeline, integrating state-of-the art algorithms and industry-standard software solutions. Incorporation of rigorous quality control steps throughout the workflow of the pipeline ensures the consistency, validity and accuracy of results. The highest relevance in the reported variants is achieved through elimination of false positive findings based on variability data for thousands of publicly available human reference sequences and validation against our in-house curated mutation database as well as the most current and relevant human mutation databases. Reference databases currently used are the 1000 Genomes Project (, the NHLBI GO Exome Sequencing Project (ESP;, the Exome Aggregation Consortium (ExAC;, ClinVar database of genotype-phenotype associations ( and the Human Gene Mutation Database ( The consequence of variants in coding and splice regions are estimated using the following in silico variant prediction tools: SIFT (, Polyphen (, and Mutation Taster (

Through our online ordering and statement reporting system, Nucleus, the customer can access specific details of the analysis of the patient. This includes coverage and quality specifications and other relevant information on the analysis. This represents our mission to build fully transparent diagnostics where the customer gains easy access to crucial details of the analysis process.

In addition to our cutting-edge patented sequencing technology and proprietary bioinformatics pipeline, we also provide the customers with the best-informed clinical report on the market. Clinical interpretation requires fundamental clinical and genetic understanding. At Blueprint Genetics our geneticists and clinicians, who together evaluate the results from the sequence analysis pipeline in the context of phenotype information provided in the requisition form, prepare the clinical statement. Our goal is to provide clinically meaningful statements that are understandable for all medical professionals, even without training in genetics.

Variants reported in the statement are always classified using the Blueprint Genetics Variant Classification Scheme modified from the ACMG guidelines (Richards et al. 2015), which has been developed by evaluating existing literature, databases and with thousands of clinical cases analyzed in our laboratory. Variant classification forms the corner stone of clinical interpretation and following patient management decisions. Our statement also includes allele frequencies in reference populations and in silico predictions. We also provide PubMed IDs to the articles or submission numbers to public databases that have been used in the interpretation of the detected variants. In our conclusion, we summarize all the existing information and provide our rationale for the classification of the variant.

A final component of the analysis is the Sanger confirmation of the variants classified as likely pathogenic or pathogenic. This does not only bring confidence to the results obtained by our NGS solution but establishes the mutation specific test for family members. Sanger sequencing is also used occasionally with other variants reported in the statement. In the case of variant of uncertain significance (VUS) we do not recommend risk stratification based on the genetic finding. Furthermore, in the case VUS we do not recommend use of genetic information in patient management or genetic counseling. For some cases Blueprint Genetics offers a special free of charge service to investigate the role of identified VUS.

We constantly follow genetic literature adapting new relevant information and findings to our diagnostics. Relevant novel discoveries can be rapidly translated and adopted into our diagnostics without delay. These processes ensure that our diagnostic panels and clinical statements remain the most up-to-date on the market.

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ICD & CPT codes

CPT codes


ICD codes

Commonly used ICD-10 codes when ordering the Cholestasis Panel

K83.1Progressive familial intrahepatic cholestasis types 1-4
E80.6Dubin-Johnson syndrome
E80.5Crigler-Najjar syndrome types 1 and 2
E80.4Gilbert syndrome
Q44.7Alagille syndrome
K83.1Intrahepatic cholestasis of pregnancy type 3
E72.2Citrullinemia type 2

Accepted sample types

  • EDTA blood, min. 1 ml
  • Purified DNA, min. 5μg
  • Saliva (Oragene DNA OG-500 kit)

Label the sample tube with your patient’s name, date of birth and the date of sample collection.

Note that we do not accept DNA samples isolated from formalin-fixed paraffin-embedded (FFPE) tissue.