rs2282335

chr9-69251016-G-Achr9-69251016-G-T

Variant summary

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

The NM_004817.4(TJP2):c.2992-19G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 1,608,104 control chromosomes in the GnomAD database, including 115,526 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (12206 hom., cov: 32)
  • Exomes 𝑓: 0.37 (103320 hom.)
• Consequence: TJP2 NM_004817.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.329

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=-0.89).
• BP6: Variant 9-69251016-G-A is Benign according to our data. Variant chr9-69251016-G-A is described in ClinVar as [Benign]. Clinvar id is 259554.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TJP2	NM_004817.4	c.2992-19G>A		intron_variant		ENST00000377245.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TJP2	ENST00000377245.9	c.2992-19G>A		intron_variant		1	NM_004817.4	P2

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59819 AN: 151822 Hom.: 12185 Cov.: 32

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.451

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.368

GnomAD3 exomes AF: 0.359 AC: 89319 AN: 248978 Hom.: 17310 AF XY: 0.367 AC XY: 49604 AN XY: 135028

Gnomad AFR exome AF: 0.449

Gnomad AMR exome AF: 0.200

Gnomad ASJ exome AF: 0.405

Gnomad EAS exome AF: 0.161

Gnomad SAS exome AF: 0.423

Gnomad FIN exome AF: 0.469

Gnomad NFE exome AF: 0.384

Gnomad OTH exome AF: 0.374

GnomAD4 exome AF: 0.372 AC: 542207 AN: 1456164 Hom.: 103320 Cov.: 31 AF XY: 0.375 AC XY: 271942 AN XY: 724930

Gnomad4 AFR exome AF: 0.454

Gnomad4 AMR exome AF: 0.211

Gnomad4 ASJ exome AF: 0.407

Gnomad4 EAS exome AF: 0.216

Gnomad4 SAS exome AF: 0.425

Gnomad4 FIN exome AF: 0.467

Gnomad4 NFE exome AF: 0.373

Gnomad4 OTH exome AF: 0.369

GnomAD4 genome AF: 0.394 AC: 59880 AN: 151940 Hom.: 12206 Cov.: 32 AF XY: 0.396 AC XY: 29404 AN XY: 74272

Gnomad4 AFR AF: 0.452

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.417

Gnomad4 EAS AF: 0.176

Gnomad4 SAS AF: 0.422

Gnomad4 FIN AF: 0.456

Gnomad4 NFE AF: 0.385

Gnomad4 OTH AF: 0.369

Alfa AF: 0.380 Hom.: 12699

Bravo AF: 0.377

Asia WGS AF: 0.335 AC: 1167 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 24, 2018	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Cholestasis, progressive familial intrahepatic, 4 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

Hypercholanemia, familial 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.11
Dann	Benign	0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2282335; hg19: chr9-71865932; COSMIC: COSV55264244; COSMIC: COSV55264244;