rs55762744
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_003331.5(TYK2):c.157G>A(p.Ala53Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00929 in 1,612,958 control chromosomes in the GnomAD database, including 95 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0072 ( 8 hom., cov: 32)
Exomes 𝑓: 0.0095 ( 87 hom. )
Consequence
TYK2
NM_003331.5 missense
NM_003331.5 missense
Scores
10
8
Clinical Significance
Conservation
PhyloP100: 4.50
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 (MetaRNN=0.0094073415).
BP6
Variant 19-10378250-C-T is Benign according to our data. Variant chr19-10378250-C-T is described in ClinVar as [Benign]. Clinvar id is 378838.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-10378250-C-T is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00723 (1100/152232) while in subpopulation NFE AF= 0.0116 (786/67988). AF 95% confidence interval is 0.0109. There are 8 homozygotes in gnomad4. There are 534 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 8 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TYK2 | NM_003331.5 | c.157G>A | p.Ala53Thr | missense_variant | 3/25 | ENST00000525621.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TYK2 | ENST00000525621.6 | c.157G>A | p.Ala53Thr | missense_variant | 3/25 | 1 | NM_003331.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00723 AC: 1100AN: 152114Hom.: 8 Cov.: 32
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GnomAD3 exomes AF: 0.00735 AC: 1839AN: 250170Hom.: 10 AF XY: 0.00785 AC XY: 1065AN XY: 135708
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GnomAD4 exome AF: 0.00950 AC: 13880AN: 1460726Hom.: 87 Cov.: 32 AF XY: 0.00952 AC XY: 6920AN XY: 726654
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GnomAD4 genome AF: 0.00723 AC: 1100AN: 152232Hom.: 8 Cov.: 32 AF XY: 0.00717 AC XY: 534AN XY: 74436
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ClinVar
Significance: Benign
Submissions summary: Benign:4
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 | Jan 29, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 23, 2017 | 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. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | TYK2: BS1, BS2 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;.;.;T
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;.;D;D;D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;M;.;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D;N
REVEL
Uncertain
Sift
Benign
D;D;D;D;D
Sift4G
Uncertain
D;D;D;.;.
Polyphen
D;D;D;.;.
Vest4
MVP
MPC
0.92
ClinPred
T
GERP RS
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gMVP
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