9-69204856-T-C

Position:

• chr9-69204856-T-C

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.61-7692T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00391 in 1,135,782 control chromosomes in the GnomAD database, including 140 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.018 (84 hom., cov: 34)
  • Exomes 𝑓: 0.0018 (56 hom.)
• Consequence: TJP2 NM_004817.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.134

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=-0.87).
• BP6: Variant 9-69204856-T-C is Benign according to our data. Variant chr9-69204856-T-C is described in ClinVar as [Benign]. Clinvar id is 1253713.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TJP2	NM_004817.4	c.61-7692T>C		intron_variant		ENST00000377245.9	NP_004808.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TJP2	ENST00000377245.9	c.61-7692T>C		intron_variant		1	NM_004817.4	ENSP00000366453	P2

Frequencies

GnomAD3 genomes AF: 0.0178 AC: 2703 AN: 152226 Hom.: 84 Cov.: 34

Gnomad AFR AF: 0.0617

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00641

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.0105

GnomAD4 exome AF: 0.00176 AC: 1735 AN: 983438 Hom.: 56 Cov.: 28 AF XY: 0.00166 AC XY: 766 AN XY: 460688

Gnomad4 AFR exome AF: 0.0651

Gnomad4 AMR exome AF: 0.00391

Gnomad4 ASJ exome AF: 0.0000969

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000150

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000154

Gnomad4 OTH exome AF: 0.00390

GnomAD4 genome AF: 0.0178 AC: 2708 AN: 152344 Hom.: 84 Cov.: 34 AF XY: 0.0169 AC XY: 1261 AN XY: 74512

Gnomad4 AFR AF: 0.0616

Gnomad4 AMR AF: 0.00640

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000323

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.0129 Hom.: 5

Bravo AF: 0.0202

Asia WGS AF: 0.00318 AC: 11 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

Dec 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.5
DANN	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs73649624; hg19: chr9-71819772;