9-69228107-C-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004817.4(TJP2):c.1446C>A(p.Asp482Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.803 in 1,606,646 control chromosomes in the GnomAD database, including 519,596 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.78 ( 46428 hom., cov: 31)

Exomes 𝑓: 0.81 ( 473168 hom. )

Consequence

TJP2
NM_004817.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.100

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]

TJP2 links:

ENSG00000285130 (HGNC:):

ENSG00000285130 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.9933616E-7).

BP6

Variant 9-69228107-C-A is Benign according to our data. Variant chr9-69228107-C-A is described in ClinVar as [Benign]. Clinvar id is 44091.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-69228107-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TJP2	NM_004817.4 link	c.1446C>A	p.Asp482Glu	missense_variant	Exon 9 of 23	ENST00000377245.9	NP_004808.2	Q9UDY2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TJP2	ENST00000377245.9 link	c.1446C>A	p.Asp482Glu	missense_variant	Exon 9 of 23	1	NM_004817.4	ENSP00000366453.4		Q9UDY2-1
ENSG00000285130	ENST00000642889.1 link	c.1833C>A	p.Asp611Glu	missense_variant	Exon 11 of 25			ENSP00000493780.1		A0A2R8YDH4

Frequencies

GnomAD3 genomes

AF:

0.778

AC:

118094

AN:

151888

Hom.:

46394

Cov.:

show subpopulations

Gnomad AFR

AF:

0.661

Gnomad AMI

AF:

0.833

Gnomad AMR

AF:

0.819

Gnomad ASJ

AF:

0.830

Gnomad EAS

AF:

0.893

Gnomad SAS

AF:

0.750

Gnomad FIN

AF:

0.869

Gnomad MID

AF:

0.845

Gnomad NFE

AF:

0.813

Gnomad OTH

AF:

0.788

GnomAD3 exomes

AF:

0.812

AC:

194472

AN:

239456

Hom.:

79354

AF XY:

0.808

AC XY:

104367

AN XY:

129146

show subpopulations

Gnomad AFR exome

AF:

0.653

Gnomad AMR exome

AF:

0.864

Gnomad ASJ exome

AF:

0.822

Gnomad EAS exome

AF:

0.889

Gnomad SAS exome

AF:

0.743

Gnomad FIN exome

AF:

0.872

Gnomad NFE exome

AF:

0.812

Gnomad OTH exome

AF:

0.814

GnomAD4 exome

AF:

0.806

AC:

1171954

AN:

1454640

Hom.:

473168

Cov.:

AF XY:

0.804

AC XY:

581022

AN XY:

722790

show subpopulations

Gnomad4 AFR exome

AF:

0.657

Gnomad4 AMR exome

AF:

0.857

Gnomad4 ASJ exome

AF:

0.820

Gnomad4 EAS exome

AF:

0.910

Gnomad4 SAS exome

AF:

0.744

Gnomad4 FIN exome

AF:

0.870

Gnomad4 NFE exome

AF:

0.806

Gnomad4 OTH exome

AF:

0.799

GnomAD4 genome

AF:

0.777

AC:

118179

AN:

152006

Hom.:

46428

Cov.:

AF XY:

0.780

AC XY:

57949

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.662

Gnomad4 AMR

AF:

0.820

Gnomad4 ASJ

AF:

0.830

Gnomad4 EAS

AF:

0.893

Gnomad4 SAS

AF:

0.750

Gnomad4 FIN

AF:

0.869

Gnomad4 NFE

AF:

0.813

Gnomad4 OTH

AF:

0.788

Alfa

AF:

0.805

Hom.:

115053

Bravo

AF:

0.769

TwinsUK

AF:

0.797

AC:

2957

ALSPAC

AF:

0.801

AC:

3087

ESP6500AA

AF:

0.658

AC:

2898

ESP6500EA

AF:

0.809

AC:

6961

ExAC

AF:

0.800

AC:

97085

Asia WGS

AF:

0.820

AC:

2851

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 09, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Asp459Glu in Exon 10 of TJP2: This variant is not expected to have clinical sign ificance because it has been identified in 34.3% (1284/3738) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs2309428). -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Cholestasis, progressive familial intrahepatic, 4

Benign:1

Sep 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hypercholanemia, familial 1

Benign:1

Sep 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.78

CADD

Benign

3.9

DANN

Benign

0.21

DEOGEN2

Benign

0.11

.;.;.;.;T;.;T;.;.;.;.;.;.;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.51

T;T;T;T;.;T;T;T;T;T;T;T;T;T

MetaRNN

Benign

9.0e-7

T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.48

.;.;.;.;N;N;N;.;.;.;.;.;.;.

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.080

.;N;.;.;.;N;N;.;.;.;N;.;N;.

REVEL

Benign

0.015

Sift

Benign

1.0

.;T;.;.;.;T;T;.;.;.;T;.;T;.

Sift4G

Benign

1.0

.;T;.;.;.;T;T;.;.;.;T;.;T;.

Polyphen

0.0

.;.;.;.;B;B;B;.;.;.;.;.;.;.

Vest4

0.038, 0.023, 0.040, 0.063

MutPred

0.21

.;.;.;.;Gain of glycosylation at P484 (P = 0.0859);Gain of glycosylation at P484 (P = 0.0859);Gain of glycosylation at P484 (P = 0.0859);Gain of glycosylation at P484 (P = 0.0859);Gain of glycosylation at P484 (P = 0.0859);.;.;.;.;.;

MPC

0.18

ClinPred

0.00067

GERP RS

-1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.051

gMVP

0.12

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over