9-69174357-G-T

Variant names:

• chr9-69174357-G-T
• rs199557806
• NM_004817.4:c.-16G>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BS2_Supporting

The NM_004817.4(TJP2):​c.-16G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000596 in 1,551,550 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0029 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00035 (5 hom.)
• Consequence: TJP2 NM_004817.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0550

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]

ENSG00000285130 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 9-69174357-G-T is Benign according to our data. Variant chr9-69174357-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 259548.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TJP2	NM_004817.4	c.-16G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 23	ENST00000377245.9	NP_004808.2
TJP2	NM_004817.4	c.-16G>T		5_prime_UTR_variant	Exon 1 of 23	ENST00000377245.9	NP_004808.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TJP2	ENST00000377245	c.-16G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 23	1	NM_004817.4	ENSP00000366453.4
TJP2	ENST00000377245	c.-16G>T		5_prime_UTR_variant	Exon 1 of 23	1	NM_004817.4	ENSP00000366453.4
ENSG00000285130	ENST00000642889.1	c.447+22586G>T		intron_variant	Intron 3 of 24			ENSP00000493780.1

Frequencies

GnomAD3 genomes AF: 0.00285 AC: 434 AN: 152218 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00987

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.000750 AC: 117 AN: 155930 AF XY: 0.000499

Gnomad AFR exome AF: 0.0116

Gnomad AMR exome AF: 0.000565

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000227

GnomAD4 exome AF: 0.000349 AC: 489 AN: 1399214 Hom.: 5 Cov.: 35 AF XY: 0.000303 AC XY: 209 AN XY: 690188

Gnomad4 AFR exome AF: 0.0127 AC: 403 AN: 31646

Gnomad4 AMR exome AF: 0.000560 AC: 20 AN: 35724

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 25166

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 35770

Gnomad4 SAS exome AF: 0.0000126 AC: 1 AN: 79254

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 49150

Gnomad4 NFE exome AF: 0.0000102 AC: 11 AN: 1078944

Gnomad4 Remaining exome AF: 0.000897 AC: 52 AN: 57980

GnomAD4 genome AF: 0.00286 AC: 435 AN: 152336 Hom.: 2 Cov.: 33 AF XY: 0.00295 AC XY: 220 AN XY: 74486

Gnomad4 AFR AF: 0.00986 AC: 0.00986051 AN: 0.00986051

Gnomad4 AMR AF: 0.00137 AC: 0.00137219 AN: 0.00137219

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.0000294 AC: 0.0000293971 AN: 0.0000293971

Gnomad4 OTH AF: 0.000945 AC: 0.00094518 AN: 0.00094518

Alfa AF: 0.000471 Hom.: 0

Bravo AF: 0.00349

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Jul 17, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	10
DANN	Benign	0.87
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs199557806; hg19: chr9-71789273;