rs11788754
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_004817.4(TJP2):c.2646G>A(p.Ala882=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0175 in 1,614,012 control chromosomes in the GnomAD database, including 304 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.013 ( 21 hom., cov: 32)
Exomes 𝑓: 0.018 ( 283 hom. )
Consequence
TJP2
NM_004817.4 synonymous
NM_004817.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.342
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.38).
BP6
?
Variant 9-69246769-G-A is Benign according to our data. Variant chr9-69246769-G-A is described in ClinVar as [Benign]. Clinvar id is 44098.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.342 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0133 (2018/152254) while in subpopulation NFE AF= 0.0212 (1439/68030). AF 95% confidence interval is 0.0202. There are 21 homozygotes in gnomad4. There are 932 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 21 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TJP2 | NM_004817.4 | c.2646G>A | p.Ala882= | synonymous_variant | 18/23 | ENST00000377245.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TJP2 | ENST00000377245.9 | c.2646G>A | p.Ala882= | synonymous_variant | 18/23 | 1 | NM_004817.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0133 AC: 2018AN: 152136Hom.: 21 Cov.: 32
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GnomAD3 exomes AF: 0.0141 AC: 3534AN: 251458Hom.: 36 AF XY: 0.0152 AC XY: 2066AN XY: 135902
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GnomAD4 exome AF: 0.0180 AC: 26248AN: 1461758Hom.: 283 Cov.: 31 AF XY: 0.0181 AC XY: 13170AN XY: 727186
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GnomAD4 genome ? AF: 0.0133 AC: 2018AN: 152254Hom.: 21 Cov.: 32 AF XY: 0.0125 AC XY: 932AN XY: 74438
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 07, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Nov 19, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 07, 2012 | Ala859Ala in Exon 19 of TJP2: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 2.1% (145/7020) of Eu ropean American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs11788754). - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at