rs41305539

Positions:

Variant summary

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

The NM_004817.4(TJP2):c.382C>A(p.Gln128Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0376 in 1,612,422 control chromosomes in the GnomAD database, including 4,544 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 0.10 ( 1987 hom., cov: 33)

Exomes 𝑓: 0.031 ( 2557 hom. )

Consequence

TJP2
NM_004817.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.02

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=0.0041084588).

BP6

Variant 9-69220926-C-A is Benign according to our data. Variant chr9-69220926-C-A is described in ClinVar as [Benign]. Clinvar id is 44100.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TJP2	NM_004817.4 linkuse as main transcript	c.382C>A	p.Gln128Lys	missense_variant	5/23	ENST00000377245.9	NP_004808.2	Q9UDY2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TJP2	ENST00000377245.9 linkuse as main transcript	c.382C>A	p.Gln128Lys	missense_variant	5/23	1	NM_004817.4	ENSP00000366453.4		Q9UDY2-1
ENSG00000285130	ENST00000642889.1 linkuse as main transcript	c.769C>A	p.Gln257Lys	missense_variant	7/25			ENSP00000493780.1		A0A2R8YDH4

Frequencies

GnomAD3 genomes

AF:

0.105

AC:

15905

AN:

152190

Hom.:

1982

Cov.:

show subpopulations

Gnomad AFR

AF:

0.298

Gnomad AMI

AF:

0.0570

Gnomad AMR

AF:

0.0578

Gnomad ASJ

AF:

0.0510

Gnomad EAS

AF:

0.0492

Gnomad SAS

AF:

0.0980

Gnomad FIN

AF:

0.0365

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.0165

Gnomad OTH

AF:

0.0841

GnomAD3 exomes

AF:

0.0518

AC:

12984

AN:

250450

Hom.:

1018

AF XY:

0.0497

AC XY:

6749

AN XY:

135664

show subpopulations

Gnomad AFR exome

AF:

0.310

Gnomad AMR exome

AF:

0.0303

Gnomad ASJ exome

AF:

0.0466

Gnomad EAS exome

AF:

0.0294

Gnomad SAS exome

AF:

0.0935

Gnomad FIN exome

AF:

0.0351

Gnomad NFE exome

AF:

0.0180

Gnomad OTH exome

AF:

0.0447

GnomAD4 exome

AF:

0.0306

AC:

44654

AN:

1460114

Hom.:

2557

Cov.:

AF XY:

0.0318

AC XY:

23113

AN XY:

726352

show subpopulations

Gnomad4 AFR exome

AF:

0.308

Gnomad4 AMR exome

AF:

0.0328

Gnomad4 ASJ exome

AF:

0.0453

Gnomad4 EAS exome

AF:

0.0623

Gnomad4 SAS exome

AF:

0.0923

Gnomad4 FIN exome

AF:

0.0361

Gnomad4 NFE exome

AF:

0.0145

Gnomad4 OTH exome

AF:

0.0477

GnomAD4 genome

AF:

0.105

AC:

15937

AN:

152308

Hom.:

1987

Cov.:

AF XY:

0.105

AC XY:

7823

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.298

Gnomad4 AMR

AF:

0.0577

Gnomad4 ASJ

AF:

0.0510

Gnomad4 EAS

AF:

0.0493

Gnomad4 SAS

AF:

0.0975

Gnomad4 FIN

AF:

0.0365

Gnomad4 NFE

AF:

0.0165

Gnomad4 OTH

AF:

0.0833

Alfa

AF:

0.0416

Hom.:

506

Bravo

AF:

0.115

TwinsUK

AF:

0.0127

AC:

ALSPAC

AF:

0.0163

AC:

ESP6500AA

AF:

0.302

AC:

1328

ESP6500EA

AF:

0.0193

AC:

166

ExAC

AF:

0.0584

AC:

7087

Asia WGS

AF:

0.0820

AC:

283

AN:

3478

EpiCase

AF:

0.0199

EpiControl

AF:

0.0212

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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	Apr 30, 2012	Gln105Lys in Exon 06 of TJP2: This variant is not expected to have clinical sign ificance because it has been identified in 30.0% (1119/3736) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs41305539). -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 15, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 03, 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. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.49

DEOGEN2

Benign

0.0017

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

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.062

LIST_S2

Benign

0.80

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

MetaRNN

Benign

0.0041

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

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.6

.;.;.;.;.;.;L;L;L;.;.;.;.;.;.;.;.;.

PrimateAI

Benign

0.27

PROVEAN

Benign

0.35

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

REVEL

Benign

0.066

Sift

Benign

1.0

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

Sift4G

Benign

0.98

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

Polyphen

0.0010

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

Vest4

0.080, 0.078, 0.083, 0.13, 0.12

MPC

0.25

ClinPred

0.0022

GERP RS

2.9

Varity_R

0.063

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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