9-69197087-C-G

Variant names:

• chr9-69197087-C-G
• rs10481782
• NM_004817.4:c.61-15461C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004817.4(TJP2):​c.61-15461C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.929 in 152,012 control chromosomes in the GnomAD database, including 65,552 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.93 (65552 hom., cov: 28)
• Consequence: TJP2 NM_004817.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.484
• Publications: 2 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: 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: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000285130 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.931 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TJP2	NM_004817.4	MANE Select	c.61-15461C>G		intron	N/A	NP_004808.2
	TJP2	NM_001369871.1		c.-10+11883C>G		intron	N/A	NP_001356800.1
	TJP2	NM_001369870.1		c.-9-15461C>G		intron	N/A	NP_001356799.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TJP2	ENST00000377245.9	TSL:1 MANE Select	c.61-15461C>G		intron	N/A	ENSP00000366453.4
	ENSG00000285130	ENST00000642889.1		c.448-15461C>G		intron	N/A	ENSP00000493780.1
	TJP2	ENST00000348208.9	TSL:1	c.61-15461C>G		intron	N/A	ENSP00000345893.4

Frequencies

GnomAD3 genomes AF: 0.929 AC: 141052 AN: 151894 Hom.: 65488 Cov.: 28

Gnomad AFR AF: 0.939

Gnomad AMI AF: 0.907

Gnomad AMR AF: 0.915

Gnomad ASJ AF: 0.926

Gnomad EAS AF: 0.935

Gnomad SAS AF: 0.917

Gnomad FIN AF: 0.947

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.924

Gnomad OTH AF: 0.924

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.929 AC: 141175 AN: 152012 Hom.: 65552 Cov.: 28 AF XY: 0.930 AC XY: 69097 AN XY: 74306

African (AFR) AF: 0.939 AC: 38921 AN: 41452

American (AMR) AF: 0.915 AC: 13959 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.926 AC: 3213 AN: 3468

East Asian (EAS) AF: 0.935 AC: 4828 AN: 5164

South Asian (SAS) AF: 0.917 AC: 4403 AN: 4800

European-Finnish (FIN) AF: 0.947 AC: 10015 AN: 10580

Middle Eastern (MID) AF: 0.952 AC: 280 AN: 294

European-Non Finnish (NFE) AF: 0.924 AC: 62784 AN: 67982

Other (OTH) AF: 0.924 AC: 1945 AN: 2106

Alfa AF: 0.926 Hom.: 8114

Bravo AF: 0.927

Asia WGS AF: 0.913 AC: 3173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.78
DANN	Benign	0.55
PhyloP100		-0.48
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs10481782; hg19: chr9-71812003;