rs17062723

Positions:

• chr9-69228011-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_004817.4(TJP2):​c.1350C>T​(p.Ser450=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00415 in 1,614,096 control chromosomes in the GnomAD database, including 237 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (136 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (101 hom.)
• Consequence: TJP2 NM_004817.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.464

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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BP6: Variant 9-69228011-C-T is Benign according to our data. Variant chr9-69228011-C-T is described in ClinVar as [Benign]. Clinvar id is 165408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.464 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TJP2	NM_004817.4	c.1350C>T	p.Ser450=	synonymous_variant	9/23	ENST00000377245.9	NP_004808.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TJP2	ENST00000377245.9	c.1350C>T	p.Ser450=	synonymous_variant	9/23	1	NM_004817.4	ENSP00000366453	P2

Frequencies

GnomAD3 genomes AF: 0.0227 AC: 3450 AN: 152108 Hom.: 136 Cov.: 32

Gnomad AFR AF: 0.0790

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00799

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.0134

GnomAD3 exomes AF: 0.00574 AC: 1444 AN: 251412 Hom.: 43 AF XY: 0.00418 AC XY: 568 AN XY: 135880

Gnomad AFR exome AF: 0.0772

Gnomad AMR exome AF: 0.00391

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000255

Gnomad OTH exome AF: 0.00342

GnomAD4 exome AF: 0.00221 AC: 3235 AN: 1461872 Hom.: 101 Cov.: 31 AF XY: 0.00196 AC XY: 1424 AN XY: 727238

Gnomad4 AFR exome AF: 0.0755

Gnomad4 AMR exome AF: 0.00449

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000174

Gnomad4 FIN exome AF: 0.0000374

Gnomad4 NFE exome AF: 0.000136

Gnomad4 OTH exome AF: 0.00533

GnomAD4 genome AF: 0.0227 AC: 3462 AN: 152224 Hom.: 136 Cov.: 32 AF XY: 0.0217 AC XY: 1615 AN XY: 74434

Gnomad4 AFR AF: 0.0791

Gnomad4 AMR AF: 0.00797

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000353

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.0103 Hom.: 18

Bravo AF: 0.0258

Asia WGS AF: 0.00491 AC: 17 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	May 07, 2012	Ser427Ser in Exon 10 of TJP2: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 7.9% (294/3738) of Af rican American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs17062723). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 05, 2017	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 13, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Feb 15, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	13
DANN	Benign	0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs17062723; hg19: chr9-71842927;