VCV001164006.1 - ClinVar

NM_000463.3(UGT1A1):c.380_381insGG (p.Cys127fs)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(1)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000463.3(UGT1A1):c.380_381insGG (p.Cys127fs)

Variation ID: 1164006 Accession: VCV001164006.1

Type and length

Insertion, 2 bp

Location

Cytogenetic: 2q37.1 2: 233760666-233760667 (GRCh38) [ NCBI UCSC ] 2: 234669312-234669313 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Jun 15, 2021	Jun 15, 2021	Feb 5, 2021

HGVS

Nucleotide	Protein	Molecular consequence
NM_000463.3:c.380_381insGG MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000454.1:p.Cys127fs	frameshift
NM_001072.4:c.862-6367_862-6366insGG MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		intron variant
NM_007120.3:c.868-6367_868-6366insGG MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		intron variant
NM_019075.4:c.856-6367_856-6366insGG MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		intron variant
NM_019076.5:c.856-6367_856-6366insGG MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		intron variant
NM_019077.3:c.856-6367_856-6366insGG MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		intron variant
NM_019078.2:c.868-6367_868-6366insGG MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		intron variant
NM_019093.4:c.868-6367_868-6366insGG MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		intron variant
NM_021027.3:c.856-6367_856-6366insGG MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		intron variant
NM_205862.3:c.61-6367_61-6366insGG		intron variant
NC_000002.12:g.233760667_233760668insGG
NC_000002.11:g.234669313_234669314insGG
NG_002601.2:g.175924_175925insGG
NG_033238.1:g.5395_5396insGG
LRG_733:g.5395_5396insGG
LRG_733t1:c.380_381insGG	LRG_733p1:p.Cys127Trpfs

... more HGVS ... less HGVS

Protein change

C127fs

Other names

Canonical SPDI

NC_000002.12:233760666:G:GGG

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

protein truncation; Variation Ontology [ VariO:0015]

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

dbSNP: rs2125987009 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
UGT1A	-	-	-	GRCh38	-	589
UGT1A1		-	-	GRCh38 GRCh37	2	373
UGT1A10		-	-	GRCh38 GRCh37	-	591
UGT1A3		-	-	GRCh38 GRCh37	-	397
UGT1A4		-	-	GRCh38 GRCh37	-	423
UGT1A5		-	-	GRCh38 GRCh37	-	441
UGT1A6		-	-	GRCh38 GRCh37	-	484
UGT1A7		-	-	GRCh38 GRCh37	-	536
UGT1A8		-	-	GRCh38 GRCh37	-	619
UGT1A9		-	-	GRCh38 GRCh37	-	571

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Crigler-Najjar syndrome type 1	Pathogenic (1)	no assertion criteria provided	Feb 5, 2021	RCV001509551.2

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Feb 05, 2021)	no assertion criteria provided Method: research	Crigler-Najjar syndrome type 1 (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Neonatal Research Center, Shiraz University of Medical Science Accession: SCV001653677.1 First in ClinVar: Jun 15, 2021 Last updated: Jun 15, 2021	Comment: The c.379_380insGG; p.C127fs variant is a null variant (frameshift) in the UGT1A1 gene. Loss-of-function mutation is a known mechanism of Criglerâ€“Najjar syndrome type I (CNS-1). … (more) The c.379_380insGG; p.C127fs variant is a null variant (frameshift) in the UGT1A1 gene. Loss-of-function mutation is a known mechanism of Criglerâ€“Najjar syndrome type I (CNS-1). This variant is assumed de novo, but without confirmation of paternity and maternity. Cosegregation with CNS-1 disease in multiple affected family members in a gene definitively known to cause the disease. We identified a novel frameshift insertion mutation (c.379_380insGG; p.C127fs) in the first exon of the UGT1A1 gene in a 16 months old boy. The patient is the offspring of first-cousin couples. Proband has an affected 11 years old brother that previously treated using liver transplantation. We studied the brother of the proband and identified this mutation as a cause of CNS-1 in his brother. However, there was no affected individual in the three-generation pedigree. The protein structure homology model showed that the c.379_380insGG disrupt the reading frame and result in a truncated protein formation. (less) Age: 0-9 years Sex: male

Comment:

The c.379_380insGG; p.C127fs variant is a null variant (frameshift) in the UGT1A1 gene. Loss-of-function mutation is a known mechanism of Criglerâ€“Najjar syndrome type I (CNS-1). This variant is assumed de novo, but without confirmation of paternity and maternity. Cosegregation with CNS-1 disease in multiple affected family members in a gene definitively known to cause the disease. We identified a novel frameshift insertion mutation (c.379_380insGG; p.C127fs) in the first exon of the UGT1A1 gene in a 16 months old boy. The patient is the offspring of first-cousin couples. Proband has an affected 11 years old brother that previously treated using liver transplantation. We studied the brother of the proband and identified this mutation as a cause of CNS-1 in his brother. However, there was no affected individual in the three-generation pedigree. The protein structure homology model showed that the c.379_380insGG disrupt the reading frame and result in a truncated protein formation.

Germline Functional Evidence

Functional Help The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence	Method Help A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter.	Result Help A brief description of the result of this method for this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
protein truncation (VariO:0015)	Method not provided	Result not provided	Neonatal Research Center, Shiraz University of Medical Science Accession: SCV001653677.1

Comment:

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs2125987009 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Sep 01, 2024

ClinVar Genomic variation as it relates to human health

NM_000463.3(UGT1A1):c.380_381insGG (p.Cys127fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs2125987009 ...