rs2095876

Positions:

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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/exons	MANE	Protein	UniProt
TJP2	NM_004817.4 linkuse as main transcript	c.2727G>A	p.Ala909Ala	synonymous_variant	19/23	ENST00000377245.9	NP_004808.2	Q9UDY2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TJP2	ENST00000377245.9 linkuse as main transcript	c.2727G>A	p.Ala909Ala	synonymous_variant	19/23	1	NM_004817.4	ENSP00000366453.4		Q9UDY2-1
ENSG00000285130	ENST00000642889.1 linkuse as main transcript	c.3114G>A	p.Ala1038Ala	synonymous_variant	21/25			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

GnomAD3 exomes

AF:

0.271

AC:

68033

AN:

251108

Hom.:

11523

AF XY:

0.258

AC XY:

34970

AN XY:

135746

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 SAS exome

AF:

0.196

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

Gnomad4 AFR exome

AF:

0.174

Gnomad4 AMR exome

AF:

0.516

Gnomad4 ASJ exome

AF:

0.163

Gnomad4 EAS exome

AF:

0.434

Gnomad4 SAS exome

AF:

0.193

Gnomad4 FIN exome

AF:

0.226

Gnomad4 NFE exome

AF:

0.213

Gnomad4 OTH exome

AF:

0.221

GnomAD4 genome

AF:

0.230

AC:

34915

AN:

152082

Hom.:

4418

Cov.:

AF XY:

0.232

AC XY:

17261

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.181

Gnomad4 AMR

AF:

0.374

Gnomad4 ASJ

AF:

0.167

Gnomad4 EAS

AF:

0.440

Gnomad4 SAS

AF:

0.215

Gnomad4 FIN

AF:

0.231

Gnomad4 NFE

AF:

0.213

Gnomad4 OTH

AF:

0.239

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

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 29, 2012	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) -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 07, 2016	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 09, 2017	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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Cholestasis, progressive familial intrahepatic, 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

Hypercholanemia, familial 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Benign

0.80

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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