rs777395821
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The ENST00000525621.6(TYK2):āc.64A>Gā(p.Met22Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000992 in 1,612,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M22T) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000525621.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TYK2 | NM_003331.5 | c.64A>G | p.Met22Val | missense_variant | 3/25 | ENST00000525621.6 | NP_003322.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TYK2 | ENST00000525621.6 | c.64A>G | p.Met22Val | missense_variant | 3/25 | 1 | NM_003331.5 | ENSP00000431885 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152162Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 249284Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135424
GnomAD4 exome AF: 0.00000822 AC: 12AN: 1460384Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 726486
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152162Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74324
ClinVar
Submissions by phenotype
Immunodeficiency 35 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 12, 2017 | This sequence change replaces methionine with valine at codon 22 of the TYK2 protein (p.Met22Val). The methionine residue is weakly conserved and there is a small physicochemical difference between methionine and valine. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with TYK2-related disease. This variant is present in population databases (rs777395821, ExAC 0.01%). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at