Genetic Variant NM_004817.4:c.60+49_60+54dupAGCGTG (chr9-69174470-T-TCGTGAG) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_004817.4(TJP2):c.60+49_60+54dupAGCGTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 1,514,898 control chromosomes in the GnomAD database, including 141,229 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.42 ( 13800 hom., cov: 0)

Exomes 𝑓: 0.42 ( 127429 hom. )

Consequence

TJP2
NM_004817.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.440

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 -10 ACMG points.

BP6

Variant 9-69174470-T-TCGTGAG is Benign according to our data. Variant chr9-69174470-T-TCGTGAG is described in ClinVar as [Benign]. Clinvar id is 682800.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TJP2	NM_004817.4 link	c.60+49_60+54dupAGCGTG		intron_variant	Intron 1 of 22	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.60+38_60+39insCGTGAG		intron_variant	Intron 1 of 22	1	NM_004817.4	ENSP00000366453.4		Q9UDY2-1
ENSG00000285130	ENST00000642889.1 link	c.447+22699_447+22700insCGTGAG		intron_variant	Intron 3 of 24			ENSP00000493780.1		A0A2R8YDH4

Frequencies

GnomAD3 genomes

AF:

0.424

AC:

64070

AN:

151146

Hom.:

13775

Cov.:

show subpopulations

Gnomad AFR

AF:

0.344

Gnomad AMI

AF:

0.285

Gnomad AMR

AF:

0.544

Gnomad ASJ

AF:

0.487

Gnomad EAS

AF:

0.622

Gnomad SAS

AF:

0.386

Gnomad FIN

AF:

0.465

Gnomad MID

AF:

0.449

Gnomad NFE

AF:

0.425

Gnomad OTH

AF:

0.457

GnomAD3 exomes

AF:

0.470

AC:

70604

AN:

150138

Hom.:

17470

AF XY:

0.461

AC XY:

36605

AN XY:

79450

show subpopulations

Gnomad AFR exome

AF:

0.321

Gnomad AMR exome

AF:

0.658

Gnomad ASJ exome

AF:

0.493

Gnomad EAS exome

AF:

0.614

Gnomad SAS exome

AF:

0.380

Gnomad FIN exome

AF:

0.473

Gnomad NFE exome

AF:

0.418

Gnomad OTH exome

AF:

0.451

GnomAD4 exome

AF:

0.423

AC:

576545

AN:

1363634

Hom.:

127429

Cov.:

AF XY:

0.422

AC XY:

284665

AN XY:

674150

show subpopulations

Gnomad4 AFR exome

AF:

0.335

Gnomad4 AMR exome

AF:

0.645

Gnomad4 ASJ exome

AF:

0.487

Gnomad4 EAS exome

AF:

0.653

Gnomad4 SAS exome

AF:

0.384

Gnomad4 FIN exome

AF:

0.466

Gnomad4 NFE exome

AF:

0.409

Gnomad4 OTH exome

AF:

0.433

GnomAD4 genome

AF:

0.424

AC:

64135

AN:

151264

Hom.:

13800

Cov.:

AF XY:

0.427

AC XY:

31515

AN XY:

73810

show subpopulations

Gnomad4 AFR

AF:

0.344

Gnomad4 AMR

AF:

0.544

Gnomad4 ASJ

AF:

0.487

Gnomad4 EAS

AF:

0.622

Gnomad4 SAS

AF:

0.386

Gnomad4 FIN

AF:

0.465

Gnomad4 NFE

AF:

0.425

Gnomad4 OTH

AF:

0.462

Alfa

AF:

0.342

Hom.:

1332

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 14, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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