rs11145746

Positions:

• chr9-69219464-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004817.4(TJP2):​c.342+1105G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,176 control chromosomes in the GnomAD database, including 2,735 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.19 (2735 hom., cov: 33)
• Consequence: TJP2 NM_004817.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.610

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TJP2	NM_004817.4	c.342+1105G>A		intron_variant		ENST00000377245.9	NP_004808.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TJP2	ENST00000377245.9	c.342+1105G>A		intron_variant		1	NM_004817.4	ENSP00000366453	P2

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28373 AN: 152058 Hom.: 2734 Cov.: 33

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.00809

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.167

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.186 AC: 28379 AN: 152176 Hom.: 2735 Cov.: 33 AF XY: 0.183 AC XY: 13599 AN XY: 74400

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.206

Gnomad4 EAS AF: 0.00811

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.186

Gnomad4 NFE AF: 0.204

Gnomad4 OTH AF: 0.166

Alfa AF: 0.187 Hom.: 502

Bravo AF: 0.185

Asia WGS AF: 0.0690 AC: 239 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.9
DANN	Benign	0.74

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

Other links and lift over

dbSNP: rs11145746; hg19: chr9-71834380;