rs12720270
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_003331.5(TYK2):c.1012-36C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 1,565,406 control chromosomes in the GnomAD database, including 31,415 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.16 ( 2637 hom., cov: 33)
Exomes 𝑓: 0.19 ( 28778 hom. )
Consequence
TYK2
NM_003331.5 intron
NM_003331.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0140
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 Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
?
Variant 19-10365084-G-A is Benign according to our data. Variant chr19-10365084-G-A is described in ClinVar as [Benign]. Clinvar id is 1257593.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TYK2 | NM_003331.5 | c.1012-36C>T | intron_variant | ENST00000525621.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TYK2 | ENST00000525621.6 | c.1012-36C>T | intron_variant | 1 | NM_003331.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.165 AC: 25031AN: 152132Hom.: 2636 Cov.: 33
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GnomAD3 exomes AF: 0.209 AC: 42480AN: 203320Hom.: 5284 AF XY: 0.211 AC XY: 22981AN XY: 108938
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GnomAD4 exome AF: 0.194 AC: 274774AN: 1413156Hom.: 28778 Cov.: 32 AF XY: 0.195 AC XY: 136131AN XY: 698046
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GnomAD4 genome ? AF: 0.164 AC: 25043AN: 152250Hom.: 2637 Cov.: 33 AF XY: 0.165 AC XY: 12244AN XY: 74426
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan | Nov 12, 2023 | This variant is classified as Benign based on local population frequency. This variant was detected in 31% of patients studied by a panel of primary immunodeficiencies. Number of patients: 30. Only high quality variants are reported. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 07, 2018 | This variant is associated with the following publications: (PMID: 19567624, 31961910) - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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