9-69268308-T-C

Position:

• chr9-69268308-T-C

Variant summary

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

The ENST00000650333.1(TJP2):​c.3339-6099T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 152,062 control chromosomes in the GnomAD database, including 31,128 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 0.63 (31128 hom., cov: 32)
• Consequence: TJP2 ENST00000650333.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46

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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TJP2	ENST00000650333.1	c.3339-6099T>C		intron_variant				A2

Frequencies

GnomAD3 genomes AF: 0.633 AC: 96131 AN: 151944 Hom.: 31120 Cov.: 32

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.776

Gnomad AMR AF: 0.698

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.747

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.678

Gnomad OTH AF: 0.635

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

GnomAD4 genome AF: 0.632 AC: 96171 AN: 152062 Hom.: 31128 Cov.: 32 AF XY: 0.637 AC XY: 47330 AN XY: 74314

Gnomad4 AFR AF: 0.491

Gnomad4 AMR AF: 0.698

Gnomad4 ASJ AF: 0.690

Gnomad4 EAS AF: 0.549

Gnomad4 SAS AF: 0.765

Gnomad4 FIN AF: 0.747

Gnomad4 NFE AF: 0.678

Gnomad4 OTH AF: 0.635

Alfa AF: 0.670 Hom.: 46246

Bravo AF: 0.617

Asia WGS AF: 0.634 AC: 2204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.71
DANN	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1538579; hg19: chr9-71883224;