9-69204747-G-T

Position:

• chr9-69204747-G-T

Variant summary

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

The NM_004817.4(TJP2):​c.61-7801G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 866,480 control chromosomes in the GnomAD database, including 65,991 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.38 (11246 hom., cov: 33)
  • Exomes 𝑓: 0.39 (54745 hom.)
• Consequence: TJP2 NM_004817.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0640

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=-0.82).
• BP6: Variant 9-69204747-G-T is Benign according to our data. Variant chr9-69204747-G-T is described in ClinVar as [Benign]. Clinvar id is 1274807.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TJP2	NM_004817.4	c.61-7801G>T		intron_variant		ENST00000377245.9	NP_004808.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TJP2	ENST00000377245.9	c.61-7801G>T		intron_variant		1	NM_004817.4	ENSP00000366453	P2

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57763 AN: 151952 Hom.: 11240 Cov.: 33

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.339

GnomAD4 exome AF: 0.386 AC: 276041 AN: 714410 Hom.: 54745 AF XY: 0.388 AC XY: 128921 AN XY: 332536

Gnomad4 AFR exome AF: 0.430

Gnomad4 AMR exome AF: 0.239

Gnomad4 ASJ exome AF: 0.394

Gnomad4 EAS exome AF: 0.316

Gnomad4 SAS exome AF: 0.452

Gnomad4 FIN exome AF: 0.357

Gnomad4 NFE exome AF: 0.385

Gnomad4 OTH exome AF: 0.373

GnomAD4 genome AF: 0.380 AC: 57787 AN: 152070 Hom.: 11246 Cov.: 33 AF XY: 0.382 AC XY: 28379 AN XY: 74324

Gnomad4 AFR AF: 0.422

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.376

Gnomad4 EAS AF: 0.304

Gnomad4 SAS AF: 0.442

Gnomad4 FIN AF: 0.410

Gnomad4 NFE AF: 0.377

Gnomad4 OTH AF: 0.335

Alfa AF: 0.377 Hom.: 1836

Bravo AF: 0.368

Asia WGS AF: 0.322 AC: 1120 AN: 3476

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	-0.82
CADD	Benign	3.5
DANN	Benign	0.76

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10870017; hg19: chr9-71819663;