rs41277895

Positions:

• chr9-69226005-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_004817.4(TJP2):​c.1057-17A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00148 in 1,613,772 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00090 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0015 (1 hom.)
• Consequence: TJP2 NM_004817.4 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.35

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]

ENSG00000285130 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 9-69226005-A-G is Benign according to our data. Variant chr9-69226005-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 259549.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TJP2	NM_004817.4	c.1057-17A>G		intron_variant		ENST00000377245.9	NP_004808.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TJP2	ENST00000377245.9	c.1057-17A>G		intron_variant		1	NM_004817.4	ENSP00000366453.4
ENSG00000285130	ENST00000642889.1	c.1444-17A>G		intron_variant				ENSP00000493780.1

Frequencies

GnomAD3 genomes AF: 0.000900 AC: 137 AN: 152164 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00171

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.000877 AC: 220 AN: 250816 Hom.: 0 AF XY: 0.000995 AC XY: 135 AN XY: 135714

Gnomad AFR exome AF: 0.000500

Gnomad AMR exome AF: 0.000463

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000164

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.00160

Gnomad OTH exome AF: 0.000983

GnomAD4 exome AF: 0.00154 AC: 2257 AN: 1461490 Hom.: 1 Cov.: 31 AF XY: 0.00150 AC XY: 1089 AN XY: 727046

Gnomad4 AFR exome AF: 0.000149

Gnomad4 AMR exome AF: 0.000582

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000186

Gnomad4 FIN exome AF: 0.000243

Gnomad4 NFE exome AF: 0.00193

Gnomad4 OTH exome AF: 0.000894

GnomAD4 genome AF: 0.000900 AC: 137 AN: 152282 Hom.: 1 Cov.: 33 AF XY: 0.000900 AC XY: 67 AN XY: 74464

Gnomad4 AFR AF: 0.000361

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00171

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.000717 Hom.: 0

Bravo AF: 0.00103

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 11, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0060
DANN	Benign	0.37

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

Publications

LitVar

Other links and lift over

dbSNP: rs41277895; hg19: chr9-71840921;