9-69174347-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_004817.4(TJP2):c.-26G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00585 in 1,551,296 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0048 (5 hom., cov: 33)
  • Exomes 𝑓: 0.0060 (33 hom.)
• Consequence: TJP2 NM_004817.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.156

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 9-69174347-G-A is Benign according to our data. Variant chr9-69174347-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 508600.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TJP2	NM_004817.4	c.-26G>A		5_prime_UTR_variant	1/23	ENST00000377245.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TJP2	ENST00000377245.9	c.-26G>A		5_prime_UTR_variant	1/23	1	NM_004817.4	P2

Frequencies

GnomAD3 genomes AF: 0.00478 AC: 727 AN: 152202 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.00121

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.00464

Gnomad ASJ AF: 0.0184

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00639

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00504 AC: 785 AN: 155732 Hom.: 6 AF XY: 0.00512 AC XY: 420 AN XY: 82076

Gnomad AFR exome AF: 0.000803

Gnomad AMR exome AF: 0.00497

Gnomad ASJ exome AF: 0.0214

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000615

Gnomad FIN exome AF: 0.00156

Gnomad NFE exome AF: 0.00647

Gnomad OTH exome AF: 0.0109

GnomAD4 exome AF: 0.00596 AC: 8343 AN: 1398978 Hom.: 33 Cov.: 35 AF XY: 0.00582 AC XY: 4018 AN XY: 690054

Gnomad4 AFR exome AF: 0.00108

Gnomad4 AMR exome AF: 0.00583

Gnomad4 ASJ exome AF: 0.0203

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000530

Gnomad4 FIN exome AF: 0.00175

Gnomad4 NFE exome AF: 0.00657

Gnomad4 OTH exome AF: 0.00590

GnomAD4 genome AF: 0.00476 AC: 725 AN: 152318 Hom.: 5 Cov.: 33 AF XY: 0.00428 AC XY: 319 AN XY: 74476

Gnomad4 AFR AF: 0.00118

Gnomad4 AMR AF: 0.00464

Gnomad4 ASJ AF: 0.0184

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00132

Gnomad4 NFE AF: 0.00639

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00472 Hom.: 1

Bravo AF: 0.00535

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 05, 2018

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
BayesDel_noAF	Benign	-0.69
Cadd	Benign	8.4
Dann	Benign	0.90
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs147729271; hg19: chr9-71789263; COSMIC: COSV99601516;