9-69174033-C-A

Position:

• chr9-69174033-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000636438.1(TJP2):​c.237+22262C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 1,039,862 control chromosomes in the GnomAD database, including 92,809 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (14022 hom., cov: 33)
  • Exomes 𝑓: 0.42 (78787 hom.)
• Consequence: TJP2 ENST00000636438.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.632

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 9-69174033-C-A is Benign according to our data. Variant chr9-69174033-C-A is described in ClinVar as [Benign]. Clinvar id is 1259088.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TJP2	NM_001170414.2	c.-10+22262C>A		intron_variant
TJP2	NM_001369870.1	c.-10+22262C>A		intron_variant
TJP2	NM_001369871.1	c.-127-11054C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TJP2	ENST00000423935.6	c.-10+22262C>A		intron_variant		2
TJP2	ENST00000606364.5	c.-10+22262C>A		intron_variant		4
TJP2	ENST00000636438.1	c.237+22262C>A		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64483 AN: 151368 Hom.: 13998 Cov.: 33

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.626

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.455

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.461

GnomAD4 exome AF: 0.419 AC: 371997 AN: 888384 Hom.: 78787 Cov.: 32 AF XY: 0.418 AC XY: 172483 AN XY: 412608

Gnomad4 AFR exome AF: 0.340

Gnomad4 AMR exome AF: 0.600

Gnomad4 ASJ exome AF: 0.483

Gnomad4 EAS exome AF: 0.653

Gnomad4 SAS exome AF: 0.385

Gnomad4 FIN exome AF: 0.452

Gnomad4 NFE exome AF: 0.417

Gnomad4 OTH exome AF: 0.438

GnomAD4 genome AF: 0.426 AC: 64543 AN: 151478 Hom.: 14022 Cov.: 33 AF XY: 0.429 AC XY: 31765 AN XY: 73996

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.547

Gnomad4 ASJ AF: 0.488

Gnomad4 EAS AF: 0.626

Gnomad4 SAS AF: 0.387

Gnomad4 FIN AF: 0.469

Gnomad4 NFE AF: 0.427

Gnomad4 OTH AF: 0.466

Alfa AF: 0.273 Hom.: 645

Bravo AF: 0.433

Asia WGS AF: 0.533 AC: 1829 AN: 3436

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.70
CADD	Benign	4.4
DANN	Benign	0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7860124; hg19: chr9-71788949;