rs4493966

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_001170416.2(TJP2):c.71G>A(p.Arg24His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0429 in 1,537,142 control chromosomes in the GnomAD database, including 2,525 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.044 ( 347 hom., cov: 33)

Exomes 𝑓: 0.043 ( 2178 hom. )

Consequence

TJP2
NM_001170416.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.142

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.739829E-4).

BP6

Variant 9-69205232-G-A is Benign according to our data. Variant chr9-69205232-G-A is described in ClinVar as [Benign]. Clinvar id is 44104.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TJP2	NM_004817.4 link	c.61-7316G>A		intron_variant	Intron 1 of 22	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.61-7316G>A		intron_variant	Intron 1 of 22	1	NM_004817.4	ENSP00000366453.4		Q9UDY2-1
ENSG00000285130	ENST00000642889.1 link	c.448-7316G>A		intron_variant	Intron 3 of 24			ENSP00000493780.1		A0A2R8YDH4

Frequencies

GnomAD3 genomes

AF:

0.0436

AC:

6639

AN:

152174

Hom.:

340

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0114

Gnomad AMI

AF:

0.0658

Gnomad AMR

AF:

0.166

Gnomad ASJ

AF:

0.0334

Gnomad EAS

AF:

0.0541

Gnomad SAS

AF:

0.0429

Gnomad FIN

AF:

0.0271

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0374

Gnomad OTH

AF:

0.0574

GnomAD3 exomes

AF:

0.0738

AC:

10289

AN:

139454

Hom.:

914

AF XY:

0.0665

AC XY:

4975

AN XY:

74796

show subpopulations

Gnomad AFR exome

AF:

0.00895

Gnomad AMR exome

AF:

0.242

Gnomad ASJ exome

AF:

0.0358

Gnomad EAS exome

AF:

0.0492

Gnomad SAS exome

AF:

0.0405

Gnomad FIN exome

AF:

0.0298

Gnomad NFE exome

AF:

0.0380

Gnomad OTH exome

AF:

0.0597

GnomAD4 exome

AF:

0.0428

AC:

59259

AN:

1384850

Hom.:

2178

Cov.:

AF XY:

0.0423

AC XY:

28896

AN XY:

683356

show subpopulations

Gnomad4 AFR exome

AF:

0.00798

Gnomad4 AMR exome

AF:

0.237

Gnomad4 ASJ exome

AF:

0.0336

Gnomad4 EAS exome

AF:

0.0439

Gnomad4 SAS exome

AF:

0.0403

Gnomad4 FIN exome

AF:

0.0289

Gnomad4 NFE exome

AF:

0.0382

Gnomad4 OTH exome

AF:

0.0440

GnomAD4 genome

AF:

0.0437

AC:

6651

AN:

152292

Hom.:

347

Cov.:

AF XY:

0.0449

AC XY:

3344

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0114

Gnomad4 AMR

AF:

0.167

Gnomad4 ASJ

AF:

0.0334

Gnomad4 EAS

AF:

0.0535

Gnomad4 SAS

AF:

0.0423

Gnomad4 FIN

AF:

0.0271

Gnomad4 NFE

AF:

0.0374

Gnomad4 OTH

AF:

0.0591

Alfa

AF:

0.0400

Hom.:

191

Bravo

AF:

0.0553

TwinsUK

AF:

0.0364

AC:

135

ALSPAC

AF:

0.0361

AC:

139

ESP6500AA

AF:

0.0166

AC:

ESP6500EA

AF:

0.0371

AC:

118

ExAC

AF:

0.0330

AC:

708

Asia WGS

AF:

0.0560

AC:

194

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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. -

Feb 07, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Arg24His in Exon 01D of TJP2: This variant is not expected to have clinical sign ificance because it has been identified in 3.7% (118/3182) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS; dbSNP rs4493966). -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.1

DANN

Benign

0.80

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0039

LIST_S2

Benign

0.22

T;T;T;T

MetaRNN

Benign

0.00087

T;T;T;T

MetaSVM

Benign

-0.95

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.72

N;.;N;.

REVEL

Benign

0.028

Sift

Benign

0.29

T;.;T;.

Sift4G

Benign

0.24

T;.;T;.

Vest4

0.10

MPC

0.24

ClinPred

0.0013

GERP RS

-2.6

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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