9-69174240-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_201629.3(TJP2):c.-133C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 1,501,928 control chromosomes in the GnomAD database, including 143,103 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.43 (14110 hom., cov: 33)
  • Exomes 𝑓: 0.43 (128993 hom.)
• Consequence: TJP2 NM_201629.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.506

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 9-69174240-C-T is Benign according to our data. Variant chr9-69174240-C-T is described in ClinVar as [Benign]. Clinvar id is 1277563.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TJP2	NM_004817.4			upstream_gene_variant		ENST00000377245.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TJP2	ENST00000377245.9			upstream_gene_variant		1	NM_004817.4	P2

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64721 AN: 151880 Hom.: 14086 Cov.: 33

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.627

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.455

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.460

GnomAD4 exome AF: 0.432 AC: 583534 AN: 1349936 Hom.: 128993 Cov.: 36 AF XY: 0.431 AC XY: 283922 AN XY: 658858

Gnomad4 AFR exome AF: 0.343

Gnomad4 AMR exome AF: 0.653

Gnomad4 ASJ exome AF: 0.490

Gnomad4 EAS exome AF: 0.658

Gnomad4 SAS exome AF: 0.388

Gnomad4 FIN exome AF: 0.470

Gnomad4 NFE exome AF: 0.420

Gnomad4 OTH exome AF: 0.443

GnomAD4 genome AF: 0.426 AC: 64777 AN: 151992 Hom.: 14110 Cov.: 33 AF XY: 0.430 AC XY: 31911 AN XY: 74272

Gnomad4 AFR AF: 0.345

Gnomad4 AMR AF: 0.547

Gnomad4 ASJ AF: 0.488

Gnomad4 EAS AF: 0.627

Gnomad4 SAS AF: 0.387

Gnomad4 FIN AF: 0.469

Gnomad4 NFE AF: 0.427

Gnomad4 OTH AF: 0.465

Alfa AF: 0.426 Hom.: 1735

Bravo AF: 0.433

Asia WGS AF: 0.535 AC: 1853 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	14
Dann	Benign	0.96
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs13301644; hg19: chr9-71789156; COSMIC: COSV55270483; COSMIC: COSV55270483;