Variant ENST00000642889.1:c.447G>A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The ENST00000642889.1(ENSG00000285130):c.447G>A(p.Gln149Gln) variant causes a splice region, synonymous change. The variant allele was found at a frequency of 0.000459 in 1,232,092 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0023 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 1 hom. )

Consequence

ENSG00000285130
ENST00000642889.1 splice_region, synonymous

Scores

Splicing: ADA: 0.01170

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.47

Variant links:

Genes affected

ENSG00000285130 (HGNC:):

ENSG00000285130 links:

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 Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
TJP2	NM_001369871.1 link	c.-128G>A	splice_region_variant	Exon 2 of 25	NP_001356800.1
TJP2	NM_001369870.1 link	c.-10G>A	splice_region_variant	Exon 2 of 24	NP_001356799.1
TJP2	NM_001170414.2 link	c.-10G>A	splice_region_variant	Exon 2 of 22	NP_001163885.1	B7Z2R3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000285130	ENST00000642889.1 link	c.447G>A	p.Gln149Gln	splice_region_variant, synonymous_variant	Exon 3 of 25			ENSP00000493780.1		A0A2R8YDH4

Frequencies

GnomAD3 genomes

AF:

0.00228

AC:

347

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00780

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00240

GnomAD4 exome

AF:

0.000201

AC:

217

AN:

1079824

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

103

AN XY:

509758

show subpopulations

Gnomad4 AFR exome

AF:

0.00806

Gnomad4 AMR exome

AF:

0.000475

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000109

Gnomad4 OTH exome

AF:

0.000618

GnomAD4 genome

AF:

0.00229

AC:

348

AN:

152268

Hom.:

Cov.:

AF XY:

0.00235

AC XY:

175

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00780

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000417

Hom.:

Bravo

AF:

0.00280

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Aug 17, 2016

Eurofins Ntd Llc (ga)

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.93

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.012

dbscSNV1_RF

Benign

0.030

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