9-69248059-C-T
Position:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The ENST00000377245.9(TJP2):c.2715C>T(p.Thr905Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 1,613,470 control chromosomes in the GnomAD database, including 45,433 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.23 ( 4421 hom., cov: 32)
Exomes 𝑓: 0.23 ( 41012 hom. )
Consequence
TJP2
ENST00000377245.9 synonymous
ENST00000377245.9 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.820
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
Variant 9-69248059-C-T is Benign according to our data. Variant chr9-69248059-C-T is described in ClinVar as [Benign]. Clinvar id is 44105.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.82 with no splicing effect.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TJP2 | NM_004817.4 | c.2715C>T | p.Thr905Thr | synonymous_variant | 19/23 | ENST00000377245.9 | NP_004808.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TJP2 | ENST00000377245.9 | c.2715C>T | p.Thr905Thr | synonymous_variant | 19/23 | 1 | NM_004817.4 | ENSP00000366453.4 | ||
ENSG00000285130 | ENST00000642889.1 | c.3102C>T | p.Thr1034Thr | synonymous_variant | 21/25 | ENSP00000493780.1 |
Frequencies
GnomAD3 genomes AF: 0.230 AC: 34915AN: 152024Hom.: 4414 Cov.: 32
GnomAD3 genomes
AF:
AC:
34915
AN:
152024
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.271 AC: 67968AN: 250650Hom.: 11535 AF XY: 0.258 AC XY: 34938AN XY: 135518
GnomAD3 exomes
AF:
AC:
67968
AN:
250650
Hom.:
AF XY:
AC XY:
34938
AN XY:
135518
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.226 AC: 330185AN: 1461328Hom.: 41012 Cov.: 36 AF XY: 0.224 AC XY: 162494AN XY: 726898
GnomAD4 exome
AF:
AC:
330185
AN:
1461328
Hom.:
Cov.:
36
AF XY:
AC XY:
162494
AN XY:
726898
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.230 AC: 34941AN: 152142Hom.: 4421 Cov.: 32 AF XY: 0.232 AC XY: 17279AN XY: 74386
GnomAD4 genome
AF:
AC:
34941
AN:
152142
Hom.:
Cov.:
32
AF XY:
AC XY:
17279
AN XY:
74386
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
1080
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 09, 2017 | 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. - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 29, 2012 | Thr905Thr in exons 19E of TJP2: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, has been identified in 21% (1815/8600) of Europ ean American chromosomes and 17% (754/4406) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washing ton.edu/EVS/; dbSNP rs2282336) - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 07, 2016 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Cholestasis, progressive familial intrahepatic, 4 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 10, 2021 | - - |
Hypercholanemia, familial 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 10, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at