NM_000463.3(UGT1A1):c.1567C>T (p.Arg523Ter) AND Crigler-Najjar syndrome, type II

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 23, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003152724.1

Allele description [Variation Report for NM_000463.3(UGT1A1):c.1567C>T (p.Arg523Ter)]

NM_000463.3(UGT1A1):c.1567C>T (p.Arg523Ter)

Genes:

UGT1A:UDP glucuronosyltransferase family 1 member A complex locus [Gene - HGNC]
UGT1A10:UDP glucuronosyltransferase family 1 member A10 [Gene - OMIM - HGNC]
UGT1A1:UDP glucuronosyltransferase family 1 member A1 [Gene - OMIM - HGNC]
UGT1A3:UDP glucuronosyltransferase family 1 member A3 [Gene - OMIM - HGNC]
UGT1A4:UDP glucuronosyltransferase family 1 member A4 [Gene - OMIM - HGNC]
UGT1A5:UDP glucuronosyltransferase family 1 member A5 [Gene - OMIM - HGNC]
UGT1A6:UDP glucuronosyltransferase family 1 member A6 [Gene - OMIM - HGNC]
UGT1A7:UDP glucuronosyltransferase family 1 member A7 [Gene - OMIM - HGNC]
UGT1A8:UDP glucuronosyltransferase family 1 member A8 [Gene - OMIM - HGNC]
UGT1A9:UDP glucuronosyltransferase family 1 member A9 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q37.1

Genomic location:

Preferred name:

NM_000463.3(UGT1A1):c.1567C>T (p.Arg523Ter)

HGVS:

NC_000002.12:g.233772524C>T
NG_002601.2:g.187781C>T
NG_033238.1:g.17252C>T
NG_051337.1:g.1863C>T
NM_000463.3:c.1567C>TMANE SELECT
NM_001072.4:c.1564C>TMANE SELECT
NM_007120.3:c.1570C>TMANE SELECT
NM_019075.4:c.1558C>TMANE SELECT
NM_019076.5:c.1558C>TMANE SELECT
NM_019077.3:c.1558C>TMANE SELECT
NM_019078.2:c.1570C>TMANE SELECT
NM_019093.4:c.1570C>TMANE SELECT
NM_021027.3:c.1558C>TMANE SELECT
NM_205862.3:c.763C>T
NP_000454.1:p.Arg523Ter
NP_000454.1:p.Arg523Ter
NP_001063.2:p.Arg522Ter
NP_001063.2:p.Arg522Ter
NP_009051.1:p.Arg524Ter
NP_009051.1:p.Arg524Ter
NP_061948.1:p.Arg520Ter
NP_061948.1:p.Arg520Ter
NP_061949.3:p.Arg520Ter
NP_061949.3:p.Arg520Ter
NP_061950.2:p.Arg520Ter
NP_061950.2:p.Arg520Ter
NP_061951.1:p.Arg524Ter
NP_061951.1:p.Arg524Ter
NP_061966.1:p.Arg524Ter
NP_061966.1:p.Arg524Ter
NP_066307.1:p.Arg520Ter
NP_066307.1:p.Arg520Ter
NP_995584.1:p.Arg255Ter
NP_995584.1:p.Arg255Ter
LRG_733t1:c.1567C>T
LRG_733:g.17252C>T
LRG_733p1:p.Arg523Ter
NC_000002.11:g.234681170C>T
NM_000463.2:c.1567C>T
NM_001072.3:c.1564C>T
NM_007120.2:c.1570C>T
NM_019075.2:c.1558C>T
NM_019076.4:c.1558C>T
NM_019077.2:c.1558C>T
NM_019078.1:c.1570C>T
NM_019093.2:c.1570C>T
NM_021027.2:c.1558C>T
NM_205862.1:c.763C>T

Protein change:

R255*

Links:

dbSNP: rs770564267

NCBI 1000 Genomes Browser:

rs770564267

Molecular consequence:

NM_000463.3:c.1567C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001072.4:c.1564C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_007120.3:c.1570C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_019075.4:c.1558C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_019076.5:c.1558C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_019077.3:c.1558C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_019078.2:c.1570C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_019093.4:c.1570C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_021027.3:c.1558C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_205862.3:c.763C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Crigler-Najjar syndrome, type II
Synonyms:: HYPERBILIRUBINEMIA, CRIGLER-NAJJAR TYPE II; Crigler Najjar syndrome, type 2; Mutation in the UDP-glucuronosyl-transferase gene
Identifiers:: MONDO: MONDO:0011725; MedGen: C2931132; Orphanet: 205; OMIM: 606785

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003842064	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Feb 23, 2023)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25822733, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003842064

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Feb 23, 2023)

unknown

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Co-inheritance of G6PD and PK deficiencies in a neonate carrying a Novel UGT1A1 genotype associated to Crigler-Najjar type II syndrome.

Minucci A, Ruggiero A, Canu G, Maurizi P, De Bonis M, Concolino P, De Luca D, Capoluongo E.

Pediatr Blood Cancer. 2015 Sep;62(9):1680-1. doi: 10.1002/pbc.25500. Epub 2015 Mar 27. No abstract available.

PubMed [citation]

PMID:: 25822733

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From 3billion, SCV003842064.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.002%). This variant was predicted to result in a loss or disruption of normal protein function through protein truncation. The predicted truncated protein may be shortened by less than 10%. The variant has been reported to be associated with UGT1A1 related disorder (ClinVar ID: VCV000548505 / PMID: 25822733). However, the evidence of pathogenicity is insufficient at this time. Therefore, this variant is classified as VUS according to the recommendation of ACMG/AMP guideline.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 1, 2024

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