NM_000214.3(JAG1):c.2304C>A (p.Cys768Ter) AND Alagille syndrome due to a JAG1 point mutation

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 13, 2022
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:: RCV002519743.2

Allele description [Variation Report for NM_000214.3(JAG1):c.2304C>A (p.Cys768Ter)]

NM_000214.3(JAG1):c.2304C>A (p.Cys768Ter)

Gene:

JAG1:jagged canonical Notch ligand 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

20p12.2

Genomic location:

Preferred name:

NM_000214.3(JAG1):c.2304C>A (p.Cys768Ter)

HGVS:

NC_000020.11:g.10644903G>T
NG_007496.1:g.34144C>A
NM_000214.3:c.2304C>AMANE SELECT
NP_000205.1:p.Cys768Ter
LRG_1191t1:c.2304C>A
LRG_1191:g.34144C>A
LRG_1191p1:p.Cys768Ter
NC_000020.10:g.10625551G>T
NM_000214.2:c.2304C>A

Protein change:

C768*

Links:

dbSNP: rs755427292

NCBI 1000 Genomes Browser:

rs755427292

Molecular consequence:

NM_000214.3:c.2304C>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Alagille syndrome due to a JAG1 point mutation
Synonyms:: HEPATIC DUCTULAR HYPOPLASIA, SYNDROMATIC; Alagille syndrome 1; JAG1-Related Alagille Syndrome
Identifiers:: MONDO: MONDO:0016862; MedGen: C1956125; Orphanet: 52; OMIM: 118450

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003443945	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 13, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 24748328, 11180599, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003443945

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 13, 2022)

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	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Spectrum of JAG1 gene mutations in Polish patients with Alagille syndrome.

Jurkiewicz D, Gliwicz D, Ciara E, Gerfen J, Pelc M, Piekutowska-Abramczuk D, Kugaudo M, Chrzanowska K, Spinner NB, Krajewska-Walasek M.

J Appl Genet. 2014 Aug;55(3):329-36. doi: 10.1007/s13353-014-0212-2. Epub 2014 Apr 20.

PubMed [citation]

PMID:: 24748328
PMCID:: PMC4102774

Mutation analysis of Jagged1 (JAG1) in Alagille syndrome patients.

Colliton RP, Bason L, Lu FM, Piccoli DA, Krantz ID, Spinner NB.

Hum Mutat. 2001 Feb;17(2):151-2.

PubMed [citation]

PMID:: 11180599

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV003443945.2

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

Description

This premature translational stop signal has been observed in individual(s) with Alagille syndrome (PMID: 24748328). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Cys768*) in the JAG1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in JAG1 are known to be pathogenic (PMID: 11180599). ClinVar contains an entry for this variant (Variation ID: 234322). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site.

#	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: Mar 30, 2024

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