9-69246759-A-G
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_004817.4(TJP2):āc.2636A>Gā(p.Gln879Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000457 in 1,614,170 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.0025 ( 1 hom., cov: 33)
Exomes š: 0.00024 ( 1 hom. )
Consequence
TJP2
NM_004817.4 missense
NM_004817.4 missense
Scores
4
4
5
Clinical Significance
Conservation
PhyloP100: 9.10
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 Likely_benign. Variant got -5 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.009550691).
BP6
Variant 9-69246759-A-G is Benign according to our data. Variant chr9-69246759-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 165416.We mark this variant Likely_benign, oryginal submissions are: {Benign=3, Likely_benign=3, Uncertain_significance=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TJP2 | NM_004817.4 | c.2636A>G | p.Gln879Arg | missense_variant | 18/23 | ENST00000377245.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TJP2 | ENST00000377245.9 | c.2636A>G | p.Gln879Arg | missense_variant | 18/23 | 1 | NM_004817.4 | P2 |
Frequencies
GnomAD3 genomes AF: 0.00252 AC: 384AN: 152200Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.000648 AC: 163AN: 251476Hom.: 1 AF XY: 0.000434 AC XY: 59AN XY: 135910
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GnomAD4 exome AF: 0.000241 AC: 352AN: 1461852Hom.: 1 Cov.: 31 AF XY: 0.000208 AC XY: 151AN XY: 727226
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GnomAD4 genome AF: 0.00253 AC: 385AN: 152318Hom.: 1 Cov.: 33 AF XY: 0.00246 AC XY: 183AN XY: 74480
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:6
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:3
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 19, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 01, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2024 | TJP2: BS1:Supporting - |
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Apr 19, 2023 | BS1 - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Feb 23, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 30, 2012 | Gln856Arg in Exon 19 of TJP2: This variant is not expected to have clinical sign ificance because it has been identified in 0.7% (28/3738) of African American ch romosomes from a broad population by the NHLBI Exome Sequencing Project (http:// evs.gs.washington.edu/EVS; dbSNP rs75450131). - |
TJP2-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 09, 2023 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;.;D;D;D;D;D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Uncertain
T
Polyphen
1.0, 1.0
.;.;.;D;D;D;.;.;.;.;.;.;.
Vest4
0.86, 0.84, 0.88, 0.86, 0.76
MVP
0.91
MPC
0.79
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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