rs2309428

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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

Publications

46 publications found

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 Gene-Disease associations (from GenCC):

cholestasis, progressive familial intrahepatic, 4
Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
autosomal dominant nonsyndromic hearing loss
Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet
familial hypercholanemia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
nonsyndromic genetic hearing loss
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
hypercholanemia, familial 1
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

TJP2 links:

ENSG00000285130 (HGNC:):

ENSG00000285130 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 44091.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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

GnomAD2 exomes

AF:

0.812

AC:

194472

AN:

239456

AF XY:

0.808

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 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

African (AFR)

AF:

0.657

AC:

21892

AN:

33314

American (AMR)

AF:

0.857

AC:

37289

AN:

43490

Ashkenazi Jewish (ASJ)

AF:

0.820

AC:

21289

AN:

25972

East Asian (EAS)

AF:

0.910

AC:

35949

AN:

39506

South Asian (SAS)

AF:

0.744

AC:

63305

AN:

85100

European-Finnish (FIN)

AF:

0.870

AC:

46167

AN:

53058

Middle Eastern (MID)

AF:

0.813

AC:

4686

AN:

5762

European-Non Finnish (NFE)

AF:

0.806

AC:

893287

AN:

1108258

Other (OTH)

AF:

0.799

AC:

48090

AN:

60180

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

12905

25811

38716

51622

64527

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20806

41612

62418

83224

104030

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.777

AC:

118179

AN:

152006

Hom.:

46428

Cov.:

AF XY:

0.780

AC XY:

57949

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.662

AC:

27383

AN:

41390

American (AMR)

AF:

0.820

AC:

12508

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.830

AC:

2879

AN:

3470

East Asian (EAS)

AF:

0.893

AC:

4623

AN:

5178

South Asian (SAS)

AF:

0.750

AC:

3604

AN:

4808

European-Finnish (FIN)

AF:

0.869

AC:

9211

AN:

10594

Middle Eastern (MID)

AF:

0.854

AC:

251

AN:

294

European-Non Finnish (NFE)

AF:

0.813

AC:

55299

AN:

67990

Other (OTH)

AF:

0.788

AC:

1661

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1334

2667

4001

5334

6668

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

864

1728

2592

3456

4320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.799

Hom.:

153473

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

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). -

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. -

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

(source)

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;.;.;.;.;.;.;.

PhyloP100

-0.10

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

PromoterAI

-0.0080

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.051

gMVP

0.12

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over