rs62567129

Variant names:

• chr9-69174188-G-A
• rs62567129
• ENST00000642889.1:c.447+22417G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

Genes affected

ENSG00000285130 (HGNC:):

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: Orphanet, Ambry Genetics
• 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)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201629.3. 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_201629.3		c.-185G>A		5_prime_UTR	Exon 1 of 21	NP_963923.1	B7Z2R3
	TJP2	NM_001369871.1		c.-127-10899G>A		intron	N/A	NP_001356800.1	Q9UDY2-3
	TJP2	NM_001369870.1		c.-10+22417G>A		intron	N/A	NP_001356799.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000285130	ENST00000642889.1		c.447+22417G>A		intron	N/A	ENSP00000493780.1	A0A2R8YDH4
	TJP2	ENST00000896723.1		c.-185G>A		5_prime_UTR	Exon 1 of 22	ENSP00000566782.1
	TJP2	ENST00000896724.1		c.-185G>A		5_prime_UTR	Exon 1 of 22	ENSP00000566783.1

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

African (AFR) AF: 0.129 AC: 3168 AN: 24564

American (AMR) AF: 0.111 AC: 1800 AN: 16154

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 3620 AN: 17318

East Asian (EAS) AF: 0.00461 AC: 130 AN: 28206

South Asian (SAS) AF: 0.150 AC: 8139 AN: 54350

European-Finnish (FIN) AF: 0.188 AC: 6830 AN: 36320

Middle Eastern (MID) AF: 0.195 AC: 668 AN: 3426

European-Non Finnish (NFE) AF: 0.210 AC: 209537 AN: 999774

Other (OTH) AF: 0.186 AC: 9369 AN: 50504

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

African (AFR) AF: 0.133 AC: 5518 AN: 41492

American (AMR) AF: 0.138 AC: 2103 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 679 AN: 3472

East Asian (EAS) AF: 0.00817 AC: 42 AN: 5142

South Asian (SAS) AF: 0.133 AC: 639 AN: 4818

European-Finnish (FIN) AF: 0.178 AC: 1876 AN: 10548

Middle Eastern (MID) AF: 0.233 AC: 68 AN: 292

European-Non Finnish (NFE) AF: 0.205 AC: 13893 AN: 67898

Other (OTH) AF: 0.158 AC: 334 AN: 2112

Alfa AF: 0.179 Hom.: 287

Bravo AF: 0.163

Asia WGS AF: 0.0620 AC: 217 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	15
DANN	Benign	0.96
PhyloP100		0.73
PromoterAI		-0.10	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=98/2	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs62567129; hg19: chr9-71789104;