rs869320745
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Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_003331.5(TYK2):c.2303_2311del(p.Ser768_Glu771delinsTer) variant causes a stop gained, inframe deletion, splice region change. The variant allele was found at a frequency of 0.000000684 in 1,461,148 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
TYK2
NM_003331.5 stop_gained, inframe_deletion, splice_region
NM_003331.5 stop_gained, inframe_deletion, splice_region
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.23
Genes affected
TYK2 (HGNC:12440): (tyrosine kinase 2) This gene encodes a member of the tyrosine kinase and, more specifically, the Janus kinases (JAKs) protein families. This protein associates with the cytoplasmic domain of type I and type II cytokine receptors and promulgate cytokine signals by phosphorylating receptor subunits. It is also a component of both the type I and type III interferon signaling pathways. As such, it may play a role in anti-viral immunity. A mutation in this gene has been associated with Immunodeficiency 35. [provided by RefSeq, Sep 2020]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 19-10358002-CCCTCCCTGG-C is Pathogenic according to our data. Variant chr19-10358002-CCCTCCCTGG-C is described in ClinVar as [Pathogenic]. Clinvar id is 155930.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TYK2 | NM_003331.5 | c.2303_2311del | p.Ser768_Glu771delinsTer | stop_gained, inframe_deletion, splice_region_variant | 16/25 | ENST00000525621.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TYK2 | ENST00000525621.6 | c.2303_2311del | p.Ser768_Glu771delinsTer | stop_gained, inframe_deletion, splice_region_variant | 16/25 | 1 | NM_003331.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
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32
GnomAD3 exomes AF: 0.00000400 AC: 1AN: 249726Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135504
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461148Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 726882
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GnomAD4 genome ? Cov.: 32
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Immunodeficiency 35 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 01, 2012 | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at