NM_000463.3(UGT1A1):c.674T>G (p.Val225Gly) AND Crigler-Najjar syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Apr 27, 2017
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:: RCV000348706.6

Allele description [Variation Report for NM_000463.3(UGT1A1):c.674T>G (p.Val225Gly)]

NM_000463.3(UGT1A1):c.674T>G (p.Val225Gly)

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.674T>G (p.Val225Gly)

HGVS:

NC_000002.12:g.233760961T>G
NG_002601.2:g.176218T>G
NG_033238.1:g.5689T>G
NM_000463.3:c.674T>GMANE SELECT
NM_001072.4:c.862-6073T>GMANE SELECT
NM_007120.3:c.868-6073T>GMANE SELECT
NM_019075.4:c.856-6073T>GMANE SELECT
NM_019076.5:c.856-6073T>GMANE SELECT
NM_019077.3:c.856-6073T>GMANE SELECT
NM_019078.2:c.868-6073T>GMANE SELECT
NM_019093.4:c.868-6073T>GMANE SELECT
NM_021027.3:c.856-6073T>GMANE SELECT
NM_205862.3:c.61-6073T>G
NP_000454.1:p.Val225Gly
NP_000454.1:p.Val225Gly
LRG_733t1:c.674T>G
LRG_733:g.5689T>G
LRG_733p1:p.Val225Gly
NC_000002.11:g.234669607T>G
NM_000463.2:c.674T>G
P22309:p.Val225Gly

Protein change:

V225G

Links:

UniProtKB: P22309#VAR_026137; dbSNP: rs35003977

NCBI 1000 Genomes Browser:

rs35003977

Molecular consequence:

NM_001072.4:c.862-6073T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_007120.3:c.868-6073T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_019075.4:c.856-6073T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_019076.5:c.856-6073T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_019077.3:c.856-6073T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_019078.2:c.868-6073T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_019093.4:c.868-6073T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_021027.3:c.856-6073T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_205862.3:c.61-6073T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000463.3:c.674T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Crigler-Najjar syndrome
Identifiers:: MONDO: MONDO:0009044; MedGen: C5551003; Orphanet: 205

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000428652	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 09 May 2019)	Likely pathogenic (Apr 27, 2017)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 26697581, 11182932, 15712364 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000428652

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 09 May 2019)

Likely pathogenic
(Apr 27, 2017)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Two Different UGT1A1 Mutations causing Crigler-Najjar Syndrome types I and II in an Iranian Family.

Maruo Y, Behnam M, Ikushiro S, Nakahara S, Nouri N, Salehi M.

J Gastrointestin Liver Dis. 2015 Dec;24(4):523-6. doi: 10.15403/jgld.2014.1121.244.ugt.

PubMed [citation]

PMID:: 26697581

Crigler-Najjar syndrome type II resulting from three different mutations in the bilirubin uridine 5'-diphosphate-glucuronosyltransferase (UGT1A1) gene.

Iolascon A, Meloni A, Coppola B, Rosatelli MC.

J Med Genet. 2000 Sep;37(9):712-3. No abstract available.

PubMed [citation]

PMID:: 11182932
PMCID:: PMC1734687

See all PubMed Citations (3)

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000428652.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The UGT1A1 c.674T>G (p.Val225Gly) variant is reported in a total of six individuals with Crigler-Najjar syndrome, including five compound heterozygotes and one heterozygote in whom a second variant was not identified (Iolascon et al. 2000; Servedio et al. 2005; Maruo et al. 2015). The variant was also found in one unaffected heterozygous parent of an affected individual. The p.Val225Gly variant was absent from 150 total controls but is reported at a frequency of 0.00212 in the South Asian population of the Exome Aggregation Consortium. Enzyme activity of the p.Val225Gly variant protein was found to be 61% as compared to wild type (Maruo et al. 2015). Based on the evidence, the p.Val225Gly variant is classified as likely pathogenic for Crigler-Najjar syndrome. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

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

Last Updated: Nov 24, 2024

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