rs7027812

Variant names:

• chr9-69218371-G-T
• rs7027812
• NM_004817.4:c.342+12G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004817.4(TJP2):​c.342+12G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00344 in 1,611,122 control chromosomes in the GnomAD database, including 165 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: 32)
  • Exomes 𝑓: 0.0019 (81 hom.)
• Consequence: TJP2 NM_004817.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.472
• Publications: 1 publications found

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]

TJP2 Gene-Disease associations (from GenCC):

• cholestasis, progressive familial intrahepatic, 4

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet
• familial hypercholanemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• nonsyndromic genetic hearing loss

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• hypercholanemia, familial 1

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)

ENSG00000285130 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 9-69218371-G-T is Benign according to our data. Variant chr9-69218371-G-T is described in ClinVar as Benign. ClinVar VariationId is 178640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0603 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004817.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TJP2	NM_004817.4	MANE Select	c.342+12G>T		intron	N/A	NP_004808.2
	TJP2	NM_001170416.2		c.435+12G>T		intron	N/A	NP_001163887.1	Q9UDY2-7
	TJP2	NM_001369875.1		c.354+12G>T		intron	N/A	NP_001356804.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TJP2	ENST00000377245.9	TSL:1 MANE Select	c.342+12G>T		intron	N/A	ENSP00000366453.4	Q9UDY2-1
	ENSG00000285130	ENST00000642889.1		c.729+12G>T		intron	N/A	ENSP00000493780.1	A0A2R8YDH4
	TJP2	ENST00000348208.9	TSL:1	c.342+12G>T		intron	N/A	ENSP00000345893.4	Q9UDY2-2

Frequencies

GnomAD3 genomes AF: 0.0179 AC: 2723 AN: 152166 Hom.: 84 Cov.: 32

Gnomad AFR AF: 0.0622

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: 0.00958

GnomAD2 exomes AF: 0.00485 AC: 1217 AN: 251140 AF XY: 0.00354

Gnomad AFR exome AF: 0.0657

Gnomad AMR exome AF: 0.00316

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000220

Gnomad OTH exome AF: 0.00228

GnomAD4 exome AF: 0.00193 AC: 2810 AN: 1458838 Hom.: 81 Cov.: 28 AF XY: 0.00171 AC XY: 1238 AN XY: 725992

African (AFR) AF: 0.0650 AC: 2170 AN: 33402

American (AMR) AF: 0.00340 AC: 152 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.000139 AC: 12 AN: 86120

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00226 AC: 13 AN: 5762

European-Non Finnish (NFE) AF: 0.000172 AC: 191 AN: 1109348

Other (OTH) AF: 0.00449 AC: 271 AN: 60320

GnomAD4 genome AF: 0.0179 AC: 2732 AN: 152284 Hom.: 84 Cov.: 32 AF XY: 0.0171 AC XY: 1277 AN XY: 74486

African (AFR) AF: 0.0623 AC: 2586 AN: 41536

American (AMR) AF: 0.00640 AC: 98 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000323 AC: 22 AN: 68024

Other (OTH) AF: 0.00995 AC: 21 AN: 2110

Alfa AF: 0.00827 Hom.: 18

Bravo AF: 0.0205

Asia WGS AF: 0.00346 AC: 12 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	14
DANN	Benign	0.55
PhyloP100		0.47
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs7027812; hg19: chr9-71833287; COSMIC: COSV55271381; COSMIC: COSV55271381;