rs864321697
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Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_004817.4(TJP2):c.817del(p.Ala273ProfsTer38) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000007 in 1,428,446 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 7.0e-7 ( 0 hom. )
Consequence
TJP2
NM_004817.4 frameshift
NM_004817.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.116
Genes affected
TJP2 (HGNC:11828): (tight junction protein 2) This gene encodes a zonula occluden that is a member of the membrane-associated guanylate kinase homolog family. The encoded protein functions as a component of the tight junction barrier in epithelial and endothelial cells and is necessary for proper assembly of tight junctions. Mutations in this gene have been identified in patients with hypercholanemia, and genomic duplication of a 270 kb region including this gene causes autosomal dominant deafness-51. Alternatively spliced transcripts encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 9-69221357-CG-C is Pathogenic according to our data. Variant chr9-69221357-CG-C is described in ClinVar as [Pathogenic]. Clinvar id is 219197.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-69221357-CG-C is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TJP2 | NM_004817.4 | c.817del | p.Ala273ProfsTer38 | frameshift_variant | 5/23 | ENST00000377245.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TJP2 | ENST00000377245.9 | c.817del | p.Ala273ProfsTer38 | frameshift_variant | 5/23 | 1 | NM_004817.4 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome AF: 7.00e-7 AC: 1AN: 1428446Hom.: 0 Cov.: 33 AF XY: 0.00000141 AC XY: 1AN XY: 707946
GnomAD4 exome
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1428446
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33
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1
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707946
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Cholestasis, progressive familial intrahepatic, 4 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 01, 2015 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 08, 2017 | - - |
Computational scores
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at