9-69205092-A-G

Position:

• chr9-69205092-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_004817.4(TJP2):​c.61-7456A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.913 in 1,531,160 control chromosomes in the GnomAD database, including 639,292 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.89 (60711 hom., cov: 34)
  • Exomes 𝑓: 0.92 (578581 hom.)
• Consequence: TJP2 NM_004817.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.12

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=-0.4).
• BP6: Variant 9-69205092-A-G is Benign according to our data. Variant chr9-69205092-A-G is described in ClinVar as [Benign]. Clinvar id is 1220827.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.915 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TJP2	NM_004817.4	c.61-7456A>G		intron_variant		ENST00000377245.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TJP2	ENST00000377245.9	c.61-7456A>G		intron_variant		1	NM_004817.4	P2

Frequencies

GnomAD3 genomes AF: 0.891 AC: 135652 AN: 152178 Hom.: 60676 Cov.: 34

Gnomad AFR AF: 0.817

Gnomad AMI AF: 0.900

Gnomad AMR AF: 0.891

Gnomad ASJ AF: 0.923

Gnomad EAS AF: 0.934

Gnomad SAS AF: 0.915

Gnomad FIN AF: 0.946

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.921

Gnomad OTH AF: 0.895

GnomAD4 exome AF: 0.916 AC: 1262707 AN: 1378864 Hom.: 578581 Cov.: 49 AF XY: 0.917 AC XY: 623250 AN XY: 679574

Gnomad4 AFR exome AF: 0.816

Gnomad4 AMR exome AF: 0.911

Gnomad4 ASJ exome AF: 0.928

Gnomad4 EAS exome AF: 0.944

Gnomad4 SAS exome AF: 0.921

Gnomad4 FIN exome AF: 0.946

Gnomad4 NFE exome AF: 0.917

Gnomad4 OTH exome AF: 0.906

GnomAD4 genome AF: 0.891 AC: 135742 AN: 152296 Hom.: 60711 Cov.: 34 AF XY: 0.894 AC XY: 66583 AN XY: 74472

Gnomad4 AFR AF: 0.817

Gnomad4 AMR AF: 0.891

Gnomad4 ASJ AF: 0.923

Gnomad4 EAS AF: 0.934

Gnomad4 SAS AF: 0.915

Gnomad4 FIN AF: 0.946

Gnomad4 NFE AF: 0.921

Gnomad4 OTH AF: 0.895

Alfa AF: 0.910 Hom.: 12830

Bravo AF: 0.884

Asia WGS AF: 0.900 AC: 3129 AN: 3478

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

Jun 22, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	19
DANN	Benign	0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2498440; hg19: chr9-71820008;