rs114073289
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS1
The NM_003331.5(TYK2):c.3330G>A(p.Glu1110=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000599 in 1,613,514 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0032 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00033 ( 4 hom. )
Consequence
TYK2
NM_003331.5 synonymous
NM_003331.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0590
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 -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.42).
BP6
?
Variant 19-10351151-C-T is Benign according to our data. Variant chr19-10351151-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 380662.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.059 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00321 (487/151834) while in subpopulation AFR AF= 0.0111 (461/41460). AF 95% confidence interval is 0.0103. There are 0 homozygotes in gnomad4. There are 246 alleles in male gnomad4 subpopulation. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TYK2 | NM_003331.5 | c.3330G>A | p.Glu1110= | synonymous_variant | 24/25 | ENST00000525621.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TYK2 | ENST00000525621.6 | c.3330G>A | p.Glu1110= | synonymous_variant | 24/25 | 1 | NM_003331.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00322 AC: 489AN: 151716Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000708 AC: 178AN: 251338Hom.: 1 AF XY: 0.000567 AC XY: 77AN XY: 135868
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GnomAD4 exome AF: 0.000328 AC: 479AN: 1461680Hom.: 4 Cov.: 30 AF XY: 0.000261 AC XY: 190AN XY: 727154
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Immunodeficiency 35 Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 27, 2023 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 14, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
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
DS_AG_spliceai
Position offset: -8
Find out detailed SpliceAI scores and Pangolin per-transcript scores at