9-69248059-C-T

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

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.820
Variant links:
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
TJP2NM_004817.4 linkuse as main transcriptc.2715C>T p.Thr905Thr synonymous_variant 19/23 ENST00000377245.9 NP_004808.2 Q9UDY2-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TJP2ENST00000377245.9 linkuse as main transcriptc.2715C>T p.Thr905Thr synonymous_variant 19/231 NM_004817.4 ENSP00000366453.4 Q9UDY2-1
ENSG00000285130ENST00000642889.1 linkuse as main transcriptc.3102C>T p.Thr1034Thr synonymous_variant 21/25 ENSP00000493780.1 A0A2R8YDH4

Frequencies

GnomAD3 genomes
AF:
0.230
AC:
34915
AN:
152024
Hom.:
4414
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.182
Gnomad AMI
AF:
0.359
Gnomad AMR
AF:
0.374
Gnomad ASJ
AF:
0.168
Gnomad EAS
AF:
0.444
Gnomad SAS
AF:
0.213
Gnomad FIN
AF:
0.231
Gnomad MID
AF:
0.161
Gnomad NFE
AF:
0.213
Gnomad OTH
AF:
0.235
GnomAD3 exomes
AF:
0.271
AC:
67968
AN:
250650
Hom.:
11535
AF XY:
0.258
AC XY:
34938
AN XY:
135518
show subpopulations
Gnomad AFR exome
AF:
0.182
Gnomad AMR exome
AF:
0.537
Gnomad ASJ exome
AF:
0.164
Gnomad EAS exome
AF:
0.436
Gnomad SAS exome
AF:
0.196
Gnomad FIN exome
AF:
0.234
Gnomad NFE exome
AF:
0.215
Gnomad OTH exome
AF:
0.242
GnomAD4 exome
AF:
0.226
AC:
330185
AN:
1461328
Hom.:
41012
Cov.:
36
AF XY:
0.224
AC XY:
162494
AN XY:
726898
show subpopulations
Gnomad4 AFR exome
AF:
0.174
Gnomad4 AMR exome
AF:
0.517
Gnomad4 ASJ exome
AF:
0.164
Gnomad4 EAS exome
AF:
0.435
Gnomad4 SAS exome
AF:
0.193
Gnomad4 FIN exome
AF:
0.226
Gnomad4 NFE exome
AF:
0.213
Gnomad4 OTH exome
AF:
0.221
GnomAD4 genome
AF:
0.230
AC:
34941
AN:
152142
Hom.:
4421
Cov.:
32
AF XY:
0.232
AC XY:
17279
AN XY:
74386
show subpopulations
Gnomad4 AFR
AF:
0.182
Gnomad4 AMR
AF:
0.374
Gnomad4 ASJ
AF:
0.168
Gnomad4 EAS
AF:
0.444
Gnomad4 SAS
AF:
0.215
Gnomad4 FIN
AF:
0.231
Gnomad4 NFE
AF:
0.213
Gnomad4 OTH
AF:
0.239
Alfa
AF:
0.218
Hom.:
1840
Bravo
AF:
0.244
Asia WGS
AF:
0.311
AC:
1080
AN:
3478
EpiCase
AF:
0.207
EpiControl
AF:
0.206

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 submitterclinical testingGeneDxMay 09, 2017This 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 submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineNov 29, 2012Thr905Thr 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 submitterclinical testingEurofins Ntd Llc (ga)Nov 07, 2016- -
not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 31, 2024- -
Cholestasis, progressive familial intrahepatic, 4 Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabSep 10, 2021- -
Hypercholanemia, familial 1 Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabSep 10, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.53
CADD
Benign
11
DANN
Benign
0.70
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2282336; hg19: chr9-71862975; COSMIC: COSV55264483; API