rs1555827769
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PP5_Moderate
The NM_000214.3(JAG1):c.2774_2788delinsCCAGGGCA(p.Cys925SerfsTer18) variant causes a frameshift change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Consequence
JAG1
NM_000214.3 frameshift
NM_000214.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.60
Genes affected
JAG1 (HGNC:6188): (jagged canonical Notch ligand 1) The jagged 1 protein encoded by JAG1 is the human homolog of the Drosophilia jagged protein. Human jagged 1 is the ligand for the receptor notch 1, the latter is involved in signaling processes. Mutations that alter the jagged 1 protein cause Alagille syndrome. Jagged 1 signalling through notch 1 has also been shown to play a role in hematopoiesis. [provided by RefSeq, Nov 2019]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PP5
?
Variant 20-10641588-AGGGGTGGACGAAGC-TGCCCTGG is Pathogenic according to our data. Variant chr20-10641588-AGGGGTGGACGAAGC-TGCCCTGG is described in ClinVar as [Pathogenic]. Clinvar id is 536527.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
JAG1 | NM_000214.3 | c.2774_2788delinsCCAGGGCA | p.Cys925SerfsTer18 | frameshift_variant | 23/26 | ENST00000254958.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
JAG1 | ENST00000254958.10 | c.2774_2788delinsCCAGGGCA | p.Cys925SerfsTer18 | frameshift_variant | 23/26 | 1 | NM_000214.3 | P1 | |
JAG1 | ENST00000423891.6 | n.2640_2654delinsCCAGGGCA | non_coding_transcript_exon_variant | 21/25 | 2 | ||||
JAG1 | ENST00000617965.2 | n.3363_3377delinsCCAGGGCA | non_coding_transcript_exon_variant | 17/17 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Alagille syndrome due to a JAG1 point mutation Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 11, 2017 | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in JAG1 are known to be pathogenic (PMID: 11180599). This variant has been reported in an individual affected with Alagille syndrome (PMID: 16575836). This variant is also known as c.2773_2787delinsCCAGGGCA in the literature. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Cys925Serfs*18) in the JAG1 gene. It is expected to result in an absent or disrupted protein product. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at