rs144396411
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_004817.4(TJP2):c.334G>A(p.Ala112Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000276 in 1,613,948 control chromosomes in the GnomAD database, including 3 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: 𝑓 0.00018 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00029 ( 3 hom. )
Consequence
TJP2
NM_004817.4 missense
NM_004817.4 missense
Scores
5
8
6
Clinical Significance
Conservation
PhyloP100: 9.81
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 -9 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.057990372).
BP6
Variant 9-69218351-G-A is Benign according to our data. Variant chr9-69218351-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 597953.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=2}.
BS2
High Homozygotes in GnomAdExome4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TJP2 | NM_004817.4 | c.334G>A | p.Ala112Thr | missense_variant | 4/23 | ENST00000377245.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TJP2 | ENST00000377245.9 | c.334G>A | p.Ala112Thr | missense_variant | 4/23 | 1 | NM_004817.4 | P2 |
Frequencies
GnomAD3 genomes AF: 0.000177 AC: 27AN: 152180Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000227 AC: 57AN: 251374Hom.: 0 AF XY: 0.000250 AC XY: 34AN XY: 135840
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GnomAD4 exome AF: 0.000287 AC: 419AN: 1461650Hom.: 3 Cov.: 30 AF XY: 0.000290 AC XY: 211AN XY: 727144
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GnomAD4 genome AF: 0.000177 AC: 27AN: 152298Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74470
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:2Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 30, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 07, 2019 | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 32942997, 24752540) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 09, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
.;.;T;T;.;.;T;.;T;.;.;.;.;.;.;.;.;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;.;D;D;D;.;D;D;D;D;D;D;D;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;.;.;.;.;.;L;L;L;.;.;.;.;.;.;.;.;.
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
.;D;.;D;.;.;.;D;D;.;.;.;D;.;.;D;.;.
REVEL
Pathogenic
Sift
Uncertain
.;D;.;D;.;.;.;D;D;.;.;.;D;.;.;D;.;.
Sift4G
Uncertain
.;D;D;D;.;.;.;T;D;.;.;.;D;.;.;D;.;.
Polyphen
1.0
.;.;.;.;.;.;D;D;D;.;.;.;.;.;.;.;.;.
Vest4
0.92, 0.94, 0.90, 0.86, 0.87
MVP
0.71
MPC
0.63
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