chr2-233760233-C-CAT

Variant names:

• chr2-233760233-C-CAT
• rs3064744
• NM_007120.3:c.868-6787_868-6786dupTA

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP5 BA1

The NM_007120.3(UGT1A4):​c.868-6787_868-6786dupTA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 1,466,600 control chromosomes in the GnomAD database, including 31,217 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity,drug response,other (no stars).

• Frequency:
  • Genomes: 𝑓 0.35 (9162 hom., cov: 0)
  • Exomes 𝑓: 0.30 (22055 hom.)
• Consequence: UGT1A4 NM_007120.3 intron
• Clinical Significance: Conflicting classifications of pathogenicity; drug response; other criteria provided, conflicting classifications P:14 U:3 B:2 O:4
• Conservation: PhyloP100: 0.148

Genes affected

UGT1A4 (HGNC:12536): (UDP glucuronosyltransferase family 1 member A4) This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites. This gene is part of a complex locus that encodes several UDP-glucuronosyltransferases. The locus includes thirteen unique alternate first exons followed by four common exons. Four of the alternate first exons are considered pseudogenes. Each of the remaining nine 5' exons may be spliced to the four common exons, resulting in nine proteins with different N-termini and identical C-termini. Each first exon encodes the substrate binding site, and is regulated by its own promoter. This enzyme has some glucuronidase activity towards bilirubin, although is is more active on amines, steroids, and sapogenins. [provided by RefSeq, Jul 2008]

UGT1A5 (HGNC:12537): (UDP glucuronosyltransferase family 1 member A5) This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites. This gene is part of a complex locus that encodes several UDP-glucuronosyltransferases. The locus includes thirteen unique alternate first exons followed by four common exons. Four of the alternate first exons are considered pseudogenes. Each of the remaining nine 5' exons may be spliced to the four common exons, resulting in nine proteins with different N-termini and identical C-termini. Each first exon encodes the substrate binding site, and is regulated by its own promoter. [provided by RefSeq, Jul 2008]

UGT1A3 (HGNC:12535): (UDP glucuronosyltransferase family 1 member A3) This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites. This gene is part of a complex locus that encodes several UDP-glucuronosyltransferases. The locus includes thirteen unique alternate first exons followed by four common exons. Four of the alternate first exons are considered pseudogenes. Each of the remaining nine 5' exons may be spliced to the four common exons, resulting in nine proteins with different N-termini and identical C-termini. Each first exon encodes the substrate binding site, and is regulated by its own promoter. Substrates of this enzyme include estrone, 2-hydroxyestrone, and metabolites of benzo alpha-pyrene. [provided by RefSeq, Jul 2008]

UGT1A6 (HGNC:12538): (UDP glucuronosyltransferase family 1 member A6) This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites. This gene is part of a complex locus that encodes several UDP-glucuronosyltransferases. The locus includes thirteen unique alternate first exons followed by four common exons. Four of the alternate first exons are considered pseudogenes. Each of the remaining nine 5' exons may be spliced to the four common exons, resulting in nine proteins with different N-termini and identical C-termini. Each first exon encodes the substrate binding site, and is regulated by its own promoter. The enzyme encoded by this gene is active on phenolic and planar compounds. Alternative splicing in the unique 5' end of this gene results in two transcript variants. [provided by RefSeq, Jul 2008]

UGT1A10 (HGNC:12531): (UDP glucuronosyltransferase family 1 member A10) This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites. This gene is part of a complex locus that encodes several UDP-glucuronosyltransferases. The locus includes thirteen unique alternate first exons followed by four common exons. Four of the alternate first exons are considered pseudogenes. Each of the remaining nine 5' exons may be spliced to the four common exons, resulting in nine proteins with different N-termini and identical C-termini. Each first exon encodes the substrate binding site, and is regulated by its own promoter. The enzyme encoded by this gene has glucuronidase activity on mycophenolic acid, coumarins, and quinolines. [provided by RefSeq, Jul 2008]

UGT1A8 (HGNC:12540): (UDP glucuronosyltransferase family 1 member A8) This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites. This gene is part of a complex locus that encodes several UDP-glucuronosyltransferases. The locus includes thirteen unique alternate first exons followed by four common exons. Four of the alternate first exons are considered pseudogenes. Each of the remaining nine 5' exons may be spliced to the four common exons, resulting in nine proteins with different N-termini and identical C-termini. Each first exon encodes the substrate binding site, and is regulated by its own promoter. The enzyme encoded by this gene has glucuronidase activity with many substrates including coumarins, phenols, anthraquinones, flavones, and some opioids. [provided by RefSeq, Jul 2008]

UGT1A7 (HGNC:12539): (UDP glucuronosyltransferase family 1 member A7) This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites. This gene is part of a complex locus that encodes several UDP-glucuronosyltransferases. The locus includes thirteen unique alternate first exons followed by four common exons. Four of the alternate first exons are considered pseudogenes. Each of the remaining nine 5' exons may be spliced to the four common exons, resulting in nine proteins with different N-termini and identical C-termini. Each first exon encodes the substrate binding site, and is regulated by its own promoter. The enzyme encoded by this gene has moderate glucuronidase activity with phenols. [provided by RefSeq, Jul 2008]

UGT1A9 (HGNC:12541): (UDP glucuronosyltransferase family 1 member A9) This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites. This gene is part of a complex locus that encodes several UDP-glucuronosyltransferases. The locus includes thirteen unique alternate first exons followed by four common exons. Four of the alternate first exons are considered pseudogenes. Each of the remaining nine 5' exons may be spliced to the four common exons, resulting in nine proteins with different N-termini and identical C-termini. Each first exon encodes the substrate binding site, and is regulated by its own promoter. The enzyme encoded by this gene is active on phenols. [provided by RefSeq, Jul 2008]

UGT1A (HGNC:12529):

UGT1A1 (HGNC:12530): (UDP glucuronosyltransferase family 1 member A1) This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites. This gene is part of a complex locus that encodes several UDP-glucuronosyltransferases. The locus includes thirteen unique alternate first exons followed by four common exons. Four of the alternate first exons are considered pseudogenes. Each of the remaining nine 5' exons may be spliced to the four common exons, resulting in nine proteins with different N-termini and identical C-termini. Each first exon encodes the substrate binding site, and is regulated by its own promoter. The preferred substrate of this enzyme is bilirubin, although it also has moderate activity with simple phenols, flavones, and C18 steroids. Mutations in this gene result in Crigler-Najjar syndromes types I and II and in Gilbert syndrome. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• PP5: Variant 2-233760233-C-CAT is Pathogenic according to our data. Variant chr2-233760233-C-CAT is described in ClinVar as [Conflicting_classifications_of_pathogenicity, drug_response, other]. Clinvar id is 12275.We mark this variant Likely_pathogenic, oryginal submissions are: {Uncertain_significance=3, Benign=2, drug_response=1, Pathogenic=10, Likely_pathogenic=1, other=1}.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGT1A4	NM_007120.3	c.868-6787_868-6786dupTA		intron_variant	Intron 1 of 4	ENST00000373409.8	NP_009051.1
UGT1A5	NM_019078.2	c.868-6787_868-6786dupTA		intron_variant	Intron 1 of 4	ENST00000373414.4	NP_061951.1
UGT1A3	NM_019093.4	c.868-6787_868-6786dupTA		intron_variant	Intron 1 of 4	ENST00000482026.6	NP_061966.1
UGT1A6	NM_001072.4	c.862-6787_862-6786dupTA		intron_variant	Intron 1 of 4	ENST00000305139.11	NP_001063.2
UGT1A10	NM_019075.4	c.856-6787_856-6786dupTA		intron_variant	Intron 1 of 4	ENST00000344644.10	NP_061948.1
UGT1A8	NM_019076.5	c.856-6787_856-6786dupTA		intron_variant	Intron 1 of 4	ENST00000373450.5	NP_061949.3
UGT1A7	NM_019077.3	c.856-6787_856-6786dupTA		intron_variant	Intron 1 of 4	ENST00000373426.4	NP_061950.2
UGT1A9	NM_021027.3	c.856-6787_856-6786dupTA		intron_variant	Intron 1 of 4	ENST00000354728.5	NP_066307.1
UGT1A1	NM_000463.3	c.-55_-54insAT		upstream_gene_variant		ENST00000305208.10	NP_000454.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGT1A4	ENST00000373409.8	c.868-6801_868-6800insAT		intron_variant	Intron 1 of 4	1	NM_007120.3	ENSP00000362508.4
UGT1A5	ENST00000373414.4	c.868-6801_868-6800insAT		intron_variant	Intron 1 of 4	1	NM_019078.2	ENSP00000362513.3
UGT1A3	ENST00000482026.6	c.868-6801_868-6800insAT		intron_variant	Intron 1 of 4	1	NM_019093.4	ENSP00000418532.1
UGT1A6	ENST00000305139.11	c.862-6801_862-6800insAT		intron_variant	Intron 1 of 4	1	NM_001072.4	ENSP00000303174.6
UGT1A10	ENST00000344644.10	c.856-6801_856-6800insAT		intron_variant	Intron 1 of 4	1	NM_019075.4	ENSP00000343838.5
UGT1A9	ENST00000354728.5	c.856-6801_856-6800insAT		intron_variant	Intron 1 of 4	1	NM_021027.3	ENSP00000346768.4
UGT1A7	ENST00000373426.4	c.856-6801_856-6800insAT		intron_variant	Intron 1 of 4	1	NM_019077.3	ENSP00000362525.3
UGT1A8	ENST00000373450.5	c.856-6801_856-6800insAT		intron_variant	Intron 1 of 4	1	NM_019076.5	ENSP00000362549.4
UGT1A1	ENST00000305208.10	c.-55_-54insAT		upstream_gene_variant		1	NM_000463.3	ENSP00000304845.5

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52281 AN: 151044 Hom.: 9168 Cov.: 0

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.328

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.323

GnomAD4 exome AF: 0.301 AC: 395737 AN: 1315438 Hom.: 22055 Cov.: 33 AF XY: 0.303 AC XY: 198308 AN XY: 653658

Gnomad4 AFR exome AF: 0.345

Gnomad4 AMR exome AF: 0.283

Gnomad4 ASJ exome AF: 0.339

Gnomad4 EAS exome AF: 0.120

Gnomad4 SAS exome AF: 0.358

Gnomad4 FIN exome AF: 0.343

Gnomad4 NFE exome AF: 0.299

Gnomad4 OTH exome AF: 0.301

GnomAD4 genome AF: 0.346 AC: 52299 AN: 151162 Hom.: 9162 Cov.: 0 AF XY: 0.348 AC XY: 25718 AN XY: 73798

Gnomad4 AFR AF: 0.398

Gnomad4 AMR AF: 0.320

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.126

Gnomad4 SAS AF: 0.408

Gnomad4 FIN AF: 0.417

Gnomad4 NFE AF: 0.320

Gnomad4 OTH AF: 0.319

ClinVar

Significance: Conflicting classifications of pathogenicity; drug response; other

Submissions summary: Pathogenic:14 Uncertain:3 Benign:2 Other:4

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Pathogenic:4 Benign:1 Other:1

Sep 12, 2024

Mayo Clinic Laboratories, Mayo Clinic

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is located in the TATA box of the UGT1A1 promoter region. Variants altering TATA repeat length from its usual length of 6 TA repeats (aka (TA)6 or UGT1A1*1) are associated with Gilbert syndrome, a mild and often asymptomatic hyperbilirubinemia. This variant is present in population databases (rs34983651, gnomAD 40%), and has an allele count higher than expected for a pathogenic variant. This variant is known to be associated with Gilbert syndrome. Individuals who are heterozygous for this variant maintain approximately 70% of the residual enzyme activity (PMID: 7565971, 9435989, 16610035, 28520360). Individuals who are homozygous for this variant maintain approximately 30% residual enzyme activity and have elevated total bilirubin levels consistent with Gilbert syndrome (PMID: 7565971, 9435989, 11003624, 26467199). Compound heterozygosity for this variant and a pathogenic UGT1A1 coding variant may result in a more pronounced enzyme deficiency, higher total serum bilirubin levels, and a clinical presentation similar to Crigler-Najjar syndrome (PMID: 9639672, 11370628). This variant is also known as (TA)7 or UGT1A1*28. Studies have shown that this variant alters UGT1A1 gene expression (PMID: 9639672). For these reasons, this variant has been classified as Pathogenic. -

Jun 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

UGT1A1: PS3, PS4, PP4:Moderate -

Nov 29, 2022

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The UGT1A1 TATA box commonly has 6 TA repeats; however, there can be 5 TA repeats, 7 TA repeats, or less commonly, 8 and 9 TA repeats (Barbarino 2014). In vitro studies have shown that UGT1A1 promoter expression decreases as the number of TA repeats increases (Beutler 1998). Genotypes that are homozygous for (TA)7, homozygous for (TA)8, or compound heterozygotes for (TA)7, (TA)8, or (TA)9 cause reduced expression of UGT1A1 and are associated with Gilbert syndrome, which is characterized by increased bilirubin levels, and may have a neonatal appearance of hereditary spherocytosis (Bosma 1995, Iolascon 1998, Nikolac 2008, Ostanek 2007). Individuals who are heterozygous for the (TA)7 *28 promoter variant may have an increased risk for drug toxicity when treated with irinotecan (Marcuello 2004, Riera 2018). Individuals who are homozygous for (TA)7 or compound heterozygous for more than 6 TA repeats may experience an increased incidence of atazanavir-associated hyperbilirubinemia (Gammal 2016). References Barbarino JM et al. PharmGKB summary: very important pharmacogene information for UGT1A1. Pharmacogenet Genomics. 2014 24:177-183. PMID: 24492252 Beutler E et al. Racial variability in the UDP-glucuronosyltransferase 1 (UGT1A1) promoter: a balanced polymorphism for regulation of bilirubin metabolism? Proc Natl Acad Sci U S A. 1998 95:8170-8174. PMID: 9653159 Bosma PJ et al. The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert's syndrome. N Engl J Med. 1995 333:1171-1175. PMID: 7565971 Gammal RS et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for UGT1A1 and Atazanavir Prescribing. Clin Pharmacol Ther. 2016 99:363-369. PMID: 26417955 Iolascon A et al. UGT1 promoter polymorphism accounts for increased neonatal appearance of hereditary spherocytosis. Blood. 1998 91:1093. PMID: 9446675 Marcuello E et al. UGT1A1 gene variations and irinotecan treatment in patients with metastatic colorectal cancer. Br J Cancer. 2004 91:678-682. PMID: 15280927 Nikolac N et al. Rare TA repeats in promoter TATA box of the UDP glucuronosyltranferase (UGT1A1) gene in Croatian subjects. Clin Chem Lab Med. 2008 46:174-178. PMID: 18324905 Ostanek B et al. UGT1A1(TA)n promoter polymorphism--a new case of a (TA)8 allele in Caucasians. Blood Cells Mol Dis. 2007 38:78-82. PMID: 17196409 Riera P et al. Relevance of CYP3A4*20, UGT1A1*37 and UGT1A1*28 variants in irinotecan-induced severe toxicity. Br J Clin Pharmacol. 2018 84:1389-1392. PMID: 29504153 -

Feb 10, 2021

Genetic Services Laboratory, University of Chicago

Significance: other

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- Reduced function allele

Oct 02, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Gilbert syndrome Pathogenic:3 Uncertain:1 Other:1

-

Centogene AG - the Rare Disease Company

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 12, 2022

Institute of Human Genetics, University of Leipzig Medical Center

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Criteria applied: PS3,PS4,PM3 -

Apr 01, 2009

OMIM

Significance: Affects

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Aug 01, 2021

Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant in the promoter region of UGT1A1 is associated with reduced transcription of UGT1A1 (Hsieh TY et al 2007). -

Crigler-Najjar syndrome, type II Pathogenic:3

-

Department of Traditional Chinese Medicine, Fujian Provincial Hospital

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: research

NM_000463.3 (UGT1A1) : c.-41_-40dupTA is a non-coding region variant, which has been reported in the literature to be detected in samples from patients with the same phenotype (PMID:7565971,9435989,11003624,26467199,9639672,11370628), and heterozygous individuals for this variant retain approximately 70% residual enzyme activity, pure heterozygous individuals retain about 30% residual enzyme activity and have elevated total bilirubin levels, and compound heterozygous individuals develop more severe enzyme defects and elevated total bilirubin levels (PMID:7565971,9435989,16610035,28520360,9639672,11370628).We detected this mutation in a patient exhibiting clinical signs of hyperbilirubinemia, who was diagnosed with Crigler-Najjar syndrome type 2 (OMIM: 606785). In accordance with the ACMG standards, this mutation aligns with PS3 (Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product) and PM3 (For recessive disorders, detected in trans with a pathogenic variant.), so we classified it as a potentially pathogenic mutation. -

Apr 01, 2009

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Jun 19, 2023

Mendelics

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Uncertain:1 Benign:1

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Lucey-Driscoll syndrome Pathogenic:1

Apr 01, 2009

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Crigler-Najjar syndrome Pathogenic:1

Oct 04, 2024

Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: research

PS3_VeryStrong, PM4, PP4 -

UGT1A1-related disorder Pathogenic:1

Dec 19, 2024

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant summary: UGT1A1 c.-41_-40dupTA is located in the untranscribed region upstream of the UGT1A1 gene region and results in the addition of 2 extra bases (TA) in the TATAA element of the gene, creating 7 TA repeats as opposed to the normal 6 TA repeats. The variant allele was found at a frequency of 0.35 in 30582 control chromosomes in the gnomAD database, including 1778 homozygotes. The observed variant frequency exceeds the estimated maximal expected allele frequency for a pathogenic variant in UGT1A1. However, this variant has been associated with Gilbert's syndrome, a mild unconjugated hyperbilirubinaemia in the absence of liver disease or overt hemolysis, which may frequently be undiagnosed and has been estimated to affect 2-12% of the general population (e.g. Monaghan_1996, Bosma_1995). The variant has been reported in multiple homozygous individuals with Gilbert's syndrome and also in unaffected homozygous individuals, although in at least one study, homozygotes who were initially thought to be unaffected were indeed found to have Gilbert's syndrome following assessment with a fasting test (e.g. Bosma_1995, Monaghan_1996). Additionally, this variant has been reported in the compound heterozygous state in trans with structural UGT1A1 variants in affected individuals with intermediate levels of unconjugated hyperbilirubinaemia (e.g. Kadakol_2001). These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function and has shown that expansion of the TATAA element to 7 TA repeats results in reduced gene expression, 18-33% of the normal TATAA element with 6 TA repeats (e.g. Bosma_1995). The following publications have been ascertained in the context of this evaluation (PMID: 7565971, 8596320, 11370628). ClinVar contains an entry for this variant (Variation ID: 12275). Based on the evidence outlined above, the variant was classified as pathogenic. -

Crigler-Najjar syndrome type 1 Pathogenic:1

Oct 04, 2020

Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Crigler-Najjar syndrome type 1;C0017551:Gilbert syndrome;C0270210:Lucey-Driscoll syndrome;C1866173:Bilirubin, serum level of, quantitative trait locus 1;C2931132:Crigler-Najjar syndrome, type II Uncertain:1

-

Juno Genomics, Hangzhou Juno Genomics, Inc

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

BS1+PS3_Supporting+PM3+PP4 -

Irinotecan response Other:1

Apr 04, 2018

Medical Genetics Summaries

Significance: drug response

Review Status: criteria provided, single submitter

Collection Method: curation

The risk of irinotecan toxicity increases with genetic variants associated with reduced UGT enzyme activity, such as UGT1A1*28. The presence of this variant results in reduced excretion of irinotecan metabolites, which leads to increased active irinotecan metabolites in the blood. Homozygous individuals (UGT1A1 *28/*28) are more likely to develop neutropenia following irinotecan therapy Poor metabolizer

Bilirubin, serum level of, quantitative trait locus 1 Other:1

Apr 01, 2009

OMIM

Significance: association

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3064744; hg19: chr2-234668879;