NM_000463.3(UGT1A1):c.622_625dup (p.Arg209fs) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Mar 18, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000598144.6

Allele description [Variation Report for NM_000463.3(UGT1A1):c.622_625dup (p.Arg209fs)]

NM_000463.3(UGT1A1):c.622_625dup (p.Arg209fs)

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:

Duplication

Cytogenetic location:

2q37.1

Genomic location:

Preferred name:

NM_000463.3(UGT1A1):c.622_625dup (p.Arg209fs)

HGVS:

NC_000002.12:g.233760909_233760912dup
NG_002601.2:g.176166_176169dup
NG_033238.1:g.5637_5640dup
NM_000463.3:c.622_625dupMANE SELECT
NM_001072.4:c.862-6125_862-6122dupMANE SELECT
NM_007120.3:c.868-6125_868-6122dupMANE SELECT
NM_019075.4:c.856-6125_856-6122dupMANE SELECT
NM_019076.5:c.856-6125_856-6122dupMANE SELECT
NM_019077.3:c.856-6125_856-6122dupMANE SELECT
NM_019078.2:c.868-6125_868-6122dupMANE SELECT
NM_019093.4:c.868-6125_868-6122dupMANE SELECT
NM_021027.3:c.856-6125_856-6122dupMANE SELECT
NM_205862.3:c.61-6125_61-6122dup
NP_000454.1:p.Arg209fs
NP_000454.1:p.Arg209fs
LRG_733t1:c.622_625dup
LRG_733:g.5637_5640dup
LRG_733p1:p.Arg209fs
NC_000002.11:g.234669554_234669555insCAGC
NC_000002.11:g.234669555_234669558dup
NM_000463.2:c.622_625dup

Protein change:

R209fs

Links:

dbSNP: rs766536479

NCBI 1000 Genomes Browser:

rs766536479

Molecular consequence:

NM_000463.3:c.622_625dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001072.4:c.862-6125_862-6122dup - intron variant - [Sequence Ontology: SO:0001627]
NM_007120.3:c.868-6125_868-6122dup - intron variant - [Sequence Ontology: SO:0001627]
NM_019075.4:c.856-6125_856-6122dup - intron variant - [Sequence Ontology: SO:0001627]
NM_019076.5:c.856-6125_856-6122dup - intron variant - [Sequence Ontology: SO:0001627]
NM_019077.3:c.856-6125_856-6122dup - intron variant - [Sequence Ontology: SO:0001627]
NM_019078.2:c.868-6125_868-6122dup - intron variant - [Sequence Ontology: SO:0001627]
NM_019093.4:c.868-6125_868-6122dup - intron variant - [Sequence Ontology: SO:0001627]
NM_021027.3:c.856-6125_856-6122dup - intron variant - [Sequence Ontology: SO:0001627]
NM_205862.3:c.61-6125_61-6122dup - intron variant - [Sequence Ontology: SO:0001627]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000706110	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Pathogenic (Feb 1, 2017)	germline	clinical testing	Citation Link,
SCV004292173	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 18, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 31145902, 23290513, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000706110

Eurofins Ntd Llc (ga)

criteria provided, single submitter

(EGL Classification Definitions 2015)

Pathogenic
(Feb 1, 2017)

germline

clinical testing

Citation Link,

SCV004292173

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 18, 2023)

germline

clinical testing

PubMed (3)
[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	germline	unknown	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Spectrum of UGT1A1 variants in Pakistani children affected with inherited unconjugated hyperbilirubinemias.

Zubaida B, Cheema HA, Hashmi MA, Naeem M.

Clin Biochem. 2019 Jul;69:30-35. doi: 10.1016/j.clinbiochem.2019.05.012. Epub 2019 May 27.

PubMed [citation]

PMID:: 31145902

UGT1A1 genetic analysis as a diagnostic aid for individuals with unconjugated hyperbilirubinemia.

Skierka JM, Kotzer KE, Lagerstedt SA, O'Kane DJ, Baudhuin LM.

J Pediatr. 2013 Jun;162(6):1146-52, 1152.e1-2. doi: 10.1016/j.jpeds.2012.11.042. Epub 2013 Jan 4.

PubMed [citation]

PMID:: 23290513

See all PubMed Citations (3)

Details of each submission

From Eurofins Ntd Llc (ga), SCV000706110.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	not provided

#	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		1	not provided	not provided	not provided

From Invitae, SCV004292173.1

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

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 437209). This premature translational stop signal has been observed in individual(s) with Crigler-Najjar syndrome type I (PMID: 31145902). This variant is present in population databases (rs766536479, gnomAD 0.01%). This sequence change creates a premature translational stop signal (p.Arg209Profs*50) in the UGT1A1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in UGT1A1 are known to be pathogenic (PMID: 23290513).

#	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: Feb 20, 2024

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