9-69174188-G-A

Position:

• chr9-69174188-G-A

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_201629.3(TJP2):​c.-185G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 1,382,578 control chromosomes in the GnomAD database, including 27,460 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2258 hom., cov: 33)
  • Exomes 𝑓: 0.20 (25202 hom.)
• Consequence: TJP2 NM_201629.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.727

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 9-69174188-G-A is Benign according to our data. Variant chr9-69174188-G-A is described in ClinVar as [Benign]. Clinvar id is 1251404.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TJP2	NM_201629.3	c.-185G>A		5_prime_UTR_variant	1/21		NP_963923.1
TJP2	XM_047424092.1	c.-341G>A		5_prime_UTR_variant	1/24		XP_047280048.1
TJP2	NM_001170414.2	c.-10+22417G>A		intron_variant			NP_001163885.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TJP2	ENST00000423935.6	c.-10+22417G>A		intron_variant		2		ENSP00000402941
TJP2	ENST00000606364.5	c.-10+22417G>A		intron_variant		4		ENSP00000475926
TJP2	ENST00000636438.1	c.237+22417G>A		intron_variant		5		ENSP00000489860	A2

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25434 AN: 151854 Hom.: 2258 Cov.: 33

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.00814

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.226

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.160

GnomAD4 exome AF: 0.198 AC: 243261 AN: 1230616 Hom.: 25202 Cov.: 38 AF XY: 0.197 AC XY: 117281 AN XY: 594276

Gnomad4 AFR exome AF: 0.129

Gnomad4 AMR exome AF: 0.111

Gnomad4 ASJ exome AF: 0.209

Gnomad4 EAS exome AF: 0.00461

Gnomad4 SAS exome AF: 0.150

Gnomad4 FIN exome AF: 0.188

Gnomad4 NFE exome AF: 0.210

Gnomad4 OTH exome AF: 0.186

GnomAD4 genome AF: 0.167 AC: 25438 AN: 151962 Hom.: 2258 Cov.: 33 AF XY: 0.164 AC XY: 12216 AN XY: 74278

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.00817

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.178

Gnomad4 NFE AF: 0.205

Gnomad4 OTH AF: 0.158

Alfa AF: 0.179 Hom.: 287

Bravo AF: 0.163

Asia WGS AF: 0.0620 AC: 217 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	15
DANN	Benign	0.96
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs62567129; hg19: chr9-71789104;