rs12720355
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_003331.5(TYK2):c.1953C>T(p.Ile651=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0136 in 1,612,786 control chromosomes in the GnomAD database, including 179 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.010 ( 17 hom., cov: 31)
Exomes 𝑓: 0.014 ( 162 hom. )
Consequence
TYK2
NM_003331.5 synonymous
NM_003331.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.44
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
?
Variant 19-10361776-G-A is Benign according to our data. Variant chr19-10361776-G-A is described in ClinVar as [Benign]. Clinvar id is 259042.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-10361776-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-2.44 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00999 (1514/151540) while in subpopulation NFE AF= 0.0159 (1077/67864). AF 95% confidence interval is 0.0151. There are 17 homozygotes in gnomad4. There are 730 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 17 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TYK2 | NM_003331.5 | c.1953C>T | p.Ile651= | synonymous_variant | 13/25 | ENST00000525621.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TYK2 | ENST00000525621.6 | c.1953C>T | p.Ile651= | synonymous_variant | 13/25 | 1 | NM_003331.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0100 AC: 1514AN: 151418Hom.: 17 Cov.: 31
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GnomAD3 exomes AF: 0.00957 AC: 2398AN: 250616Hom.: 10 AF XY: 0.00984 AC XY: 1334AN XY: 135576
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GnomAD4 exome AF: 0.0140 AC: 20398AN: 1461246Hom.: 162 Cov.: 36 AF XY: 0.0139 AC XY: 10091AN XY: 726978
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GnomAD4 genome ? AF: 0.00999 AC: 1514AN: 151540Hom.: 17 Cov.: 31 AF XY: 0.00986 AC XY: 730AN XY: 74058
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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:2
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2024 | TYK2: BP4, BP7, BS1, BS2 - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Immunodeficiency 35 Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
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