9-69174347-G-A
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Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBS2_Supporting
The ENST00000377245.9(TJP2):c.-26G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00585 in 1,551,296 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0048 ( 5 hom., cov: 33)
Exomes 𝑓: 0.0060 ( 33 hom. )
Consequence
TJP2
ENST00000377245.9 5_prime_UTR
ENST00000377245.9 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.156
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 Benign. Variant got -7 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.69).
BP6
Variant 9-69174347-G-A is Benign according to our data. Variant chr9-69174347-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 508600.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAd4 at 5 AR geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TJP2 | NM_004817.4 | c.-26G>A | 5_prime_UTR_variant | 1/23 | ENST00000377245.9 | NP_004808.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TJP2 | ENST00000377245.9 | c.-26G>A | 5_prime_UTR_variant | 1/23 | 1 | NM_004817.4 | ENSP00000366453 | P2 |
Frequencies
GnomAD3 genomes AF: 0.00478 AC: 727AN: 152202Hom.: 5 Cov.: 33
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GnomAD3 exomes AF: 0.00504 AC: 785AN: 155732Hom.: 6 AF XY: 0.00512 AC XY: 420AN XY: 82076
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GnomAD4 exome AF: 0.00596 AC: 8343AN: 1398978Hom.: 33 Cov.: 35 AF XY: 0.00582 AC XY: 4018AN XY: 690054
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GnomAD4 genome AF: 0.00476 AC: 725AN: 152318Hom.: 5 Cov.: 33 AF XY: 0.00428 AC XY: 319AN XY: 74476
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 05, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at