rs2095876

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_004817.4(TJP2):c.2727G>A(p.Ala909Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 1,613,750 control chromosomes in the GnomAD database, including 45,455 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4418 hom., cov: 32)

Exomes 𝑓: 0.23 ( 41037 hom. )

Consequence

TJP2
NM_004817.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.156

Publications

23 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.27).

BP6

Variant 9-69248071-G-A is Benign according to our data. Variant chr9-69248071-G-A is described in ClinVar as Benign. ClinVar VariationId is 44106.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.156 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TJP2	NM_004817.4 link	c.2727G>A	p.Ala909Ala	synonymous_variant	Exon 19 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.2727G>A	p.Ala909Ala	synonymous_variant	Exon 19 of 23	1	NM_004817.4	ENSP00000366453.4		Q9UDY2-1
ENSG00000285130	ENST00000642889.1 link	c.3114G>A	p.Ala1038Ala	synonymous_variant	Exon 21 of 25			ENSP00000493780.1		A0A2R8YDH4

Frequencies

GnomAD3 genomes

AF:

0.230

AC:

34889

AN:

151964

Hom.:

4411

Cov.:

show subpopulations

Gnomad AFR

AF:

0.182

Gnomad AMI

AF:

0.359

Gnomad AMR

AF:

0.374

Gnomad ASJ

AF:

0.167

Gnomad EAS

AF:

0.441

Gnomad SAS

AF:

0.213

Gnomad FIN

AF:

0.231

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.213

Gnomad OTH

AF:

0.236

GnomAD2 exomes

AF:

0.271

AC:

68033

AN:

251108

AF XY:

0.258

show subpopulations

Gnomad AFR exome

AF:

0.181

Gnomad AMR exome

AF:

0.536

Gnomad ASJ exome

AF:

0.163

Gnomad EAS exome

AF:

0.435

Gnomad FIN exome

AF:

0.234

Gnomad NFE exome

AF:

0.215

Gnomad OTH exome

AF:

0.242

GnomAD4 exome

AF:

0.226

AC:

330387

AN:

1461668

Hom.:

41037

Cov.:

AF XY:

0.224

AC XY:

162619

AN XY:

727120

show subpopulations

African (AFR)

AF:

0.174

AC:

5810

AN:

33474

American (AMR)

AF:

0.516

AC:

23061

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.163

AC:

4252

AN:

26130

East Asian (EAS)

AF:

0.434

AC:

17218

AN:

39696

South Asian (SAS)

AF:

0.193

AC:

16633

AN:

86242

European-Finnish (FIN)

AF:

0.226

AC:

12084

AN:

53390

Middle Eastern (MID)

AF:

0.159

AC:

914

AN:

5760

European-Non Finnish (NFE)

AF:

0.213

AC:

237065

AN:

1111874

Other (OTH)

AF:

0.221

AC:

13350

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

13547

27095

40642

54190

67737

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8428

16856

25284

33712

42140

<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:

0.230

AC:

34915

AN:

152082

Hom.:

4418

Cov.:

AF XY:

0.232

AC XY:

17261

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.181

AC:

7525

AN:

41504

American (AMR)

AF:

0.374

AC:

5722

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.167

AC:

578

AN:

3468

East Asian (EAS)

AF:

0.440

AC:

2264

AN:

5140

South Asian (SAS)

AF:

0.215

AC:

1035

AN:

4816

European-Finnish (FIN)

AF:

0.231

AC:

2441

AN:

10588

Middle Eastern (MID)

AF:

0.160

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.213

AC:

14471

AN:

67966

Other (OTH)

AF:

0.239

AC:

505

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1330

2660

3990

5320

6650

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

362

724

1086

1448

1810

<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:

0.198

Hom.:

1989

Bravo

AF:

0.244

Asia WGS

AF:

0.310

AC:

1077

AN:

3478

EpiCase

AF:

0.207

EpiControl

AF:

0.207

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Nov 29, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Ala909Ala in exon 19E of TJP2: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and it has been identified in 21% (1812/8600) of European American chromosomes and 17% (755/4406) of African American chromosome s from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.w ashington.edu/EVS/; dbSNP rs2095876) -

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. -

Nov 07, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

BayesDel_noAF

Benign

-0.27

CADD

Benign

(source)

DANN

Benign

0.80

PhyloP100

0.16

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Mutation Taster

=100/0

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

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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