9-69174015-C-T

Variant summary

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

The ENST00000636438.1(TJP2):c.237+22244C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00144 in 1,019,082 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0036 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (1 hom.)
• Consequence: TJP2 ENST00000636438.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.432

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 9-69174015-C-T is Benign according to our data. Variant chr9-69174015-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1213124.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TJP2	NM_001170414.2	c.-10+22244C>T		intron_variant
TJP2	NM_001369870.1	c.-10+22244C>T		intron_variant
TJP2	NM_001369871.1	c.-127-11072C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TJP2	ENST00000423935.6	c.-10+22244C>T		intron_variant		2
TJP2	ENST00000606364.5	c.-10+22244C>T		intron_variant		4
TJP2	ENST00000636438.1	c.237+22244C>T		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.00362 AC: 550 AN: 151858 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.000266

Gnomad AMI AF: 0.0396

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00518

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0147

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00455

Gnomad OTH AF: 0.00287

GnomAD4 exome AF: 0.00106 AC: 921 AN: 867116 Hom.: 1 Cov.: 29 AF XY: 0.00100 AC XY: 402 AN XY: 402066

Gnomad4 AFR exome AF: 0.000120

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00298

Gnomad4 EAS exome AF: 0.000856

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0157

Gnomad4 NFE exome AF: 0.00104

Gnomad4 OTH exome AF: 0.00132

GnomAD4 genome AF: 0.00362 AC: 550 AN: 151966 Hom.: 4 Cov.: 32 AF XY: 0.00412 AC XY: 306 AN XY: 74262

Gnomad4 AFR AF: 0.000265

Gnomad4 AMR AF: 0.000523

Gnomad4 ASJ AF: 0.00518

Gnomad4 EAS AF: 0.00117

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0147

Gnomad4 NFE AF: 0.00455

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00614 Hom.: 3

Bravo AF: 0.00216

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 18, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
Cadd	Benign	3.1
Dann	Benign	0.96
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs561839422; hg19: chr9-71788931;