rs140442228

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_004817.4(TJP2):c.2778C>T(p.Asp926Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0175 in 1,614,142 control chromosomes in the GnomAD database, including 305 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 21 hom., cov: 32)

Exomes 𝑓: 0.018 ( 284 hom. )

Consequence

TJP2
NM_004817.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0960

Publications

3 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 9-69248122-C-T is Benign according to our data. Variant chr9-69248122-C-T is described in ClinVar as Benign. ClinVar VariationId is 44107.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.096 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0132 (2013/152276) while in subpopulation NFE AF = 0.0211 (1436/68024). AF 95% confidence interval is 0.0202. There are 21 homozygotes in GnomAd4. There are 933 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 21 AD,Unknown,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TJP2	NM_004817.4 link	c.2778C>T	p.Asp926Asp	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.2778C>T	p.Asp926Asp	synonymous_variant	Exon 19 of 23	1	NM_004817.4	ENSP00000366453.4		Q9UDY2-1
ENSG00000285130	ENST00000642889.1 link	c.3165C>T	p.Asp1055Asp	synonymous_variant	Exon 21 of 25			ENSP00000493780.1		A0A2R8YDH4

Frequencies

GnomAD3 genomes

AF:

0.0132

AC:

2013

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00348

Gnomad AMI

AF:

0.00879

Gnomad AMR

AF:

0.0147

Gnomad ASJ

AF:

0.0161

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0180

Gnomad FIN

AF:

0.00217

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0211

Gnomad OTH

AF:

0.0124

GnomAD2 exomes

AF:

0.0140

AC:

3530

AN:

251392

AF XY:

0.0152

show subpopulations

Gnomad AFR exome

AF:

0.00301

Gnomad AMR exome

AF:

0.00726

Gnomad ASJ exome

AF:

0.0150

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00245

Gnomad NFE exome

AF:

0.0203

Gnomad OTH exome

AF:

0.0165

GnomAD4 exome

AF:

0.0180

AC:

26280

AN:

1461866

Hom.:

284

Cov.:

AF XY:

0.0181

AC XY:

13181

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.00370

AC:

124

AN:

33480

American (AMR)

AF:

0.00724

AC:

324

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0135

AC:

354

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39698

South Asian (SAS)

AF:

0.0191

AC:

1649

AN:

86254

European-Finnish (FIN)

AF:

0.00324

AC:

173

AN:

53410

Middle Eastern (MID)

AF:

0.0246

AC:

142

AN:

5766

European-Non Finnish (NFE)

AF:

0.0203

AC:

22620

AN:

1112002

Other (OTH)

AF:

0.0148

AC:

893

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

1531

3063

4594

6126

7657

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

838

1676

2514

3352

4190

<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:

0.0132

AC:

2013

AN:

152276

Hom.:

Cov.:

AF XY:

0.0125

AC XY:

933

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.00347

AC:

144

AN:

41552

American (AMR)

AF:

0.0147

AC:

225

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0161

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.0178

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00217

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0211

AC:

1436

AN:

68024

Other (OTH)

AF:

0.0123

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

112

223

335

446

558

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.0179

Hom.:

Bravo

AF:

0.0132

Asia WGS

AF:

0.00577

AC:

AN:

3478

EpiCase

AF:

0.0221

EpiControl

AF:

0.0228

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 07, 2018

GeneDx

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

- -

Nov 19, 2018

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Jan 08, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is not expected to have clinical significance because it does not a lter an amino acid residue and has been identified in 2.0% (173/8600) of Europea n American chromosomes and 0.5% (23/4406) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washingto n.edu/EVS; dbSNP rs140442228). -

PreventionGenetics, part of Exact Sciences

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

0.77

PhyloP100

-0.096

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.7

Mutation Taster

=97/3

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