rs140442228

Positions:

chr9-69248122-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The ENST00000377245.9(TJP2):c.2778C>T(p.Asp926=) 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
ENST00000377245.9 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0960

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TJP2	NM_004817.4 linkuse as main transcript	c.2778C>T	p.Asp926=	synonymous_variant	19/23	ENST00000377245.9	NP_004808.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TJP2	ENST00000377245.9 linkuse as main transcript	c.2778C>T	p.Asp926=	synonymous_variant	19/23	1	NM_004817.4	ENSP00000366453	P2	Q9UDY2-1

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

GnomAD3 exomes

AF:

0.0140

AC:

3530

AN:

251392

Hom.:

AF XY:

0.0152

AC XY:

2062

AN XY:

135878

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 SAS exome

AF:

0.0202

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

Gnomad4 AFR exome

AF:

0.00370

Gnomad4 AMR exome

AF:

0.00724

Gnomad4 ASJ exome

AF:

0.0135

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0191

Gnomad4 FIN exome

AF:

0.00324

Gnomad4 NFE exome

AF:

0.0203

Gnomad4 OTH exome

AF:

0.0148

GnomAD4 genome

AF:

0.0132

AC:

2013

AN:

152276

Hom.:

Cov.:

AF XY:

0.0125

AC XY:

933

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00347

Gnomad4 AMR

AF:

0.0147

Gnomad4 ASJ

AF:

0.0161

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0178

Gnomad4 FIN

AF:

0.00217

Gnomad4 NFE

AF:

0.0211

Gnomad4 OTH

AF:

0.0123

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Nov 19, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 07, 2018	- -

not specified

Benign:2

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	Jan 08, 2013	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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Benign

0.77

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.7

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

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