rs201240289
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_003331.5(TYK2):c.1141C>T(p.Arg381Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000225 in 1,614,206 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R381Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_003331.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TYK2 | NM_003331.5 | c.1141C>T | p.Arg381Trp | missense_variant | 8/25 | ENST00000525621.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TYK2 | ENST00000525621.6 | c.1141C>T | p.Arg381Trp | missense_variant | 8/25 | 1 | NM_003331.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000269 AC: 41AN: 152264Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000358 AC: 90AN: 251340Hom.: 0 AF XY: 0.000383 AC XY: 52AN XY: 135886
GnomAD4 exome AF: 0.000221 AC: 323AN: 1461824Hom.: 0 Cov.: 32 AF XY: 0.000253 AC XY: 184AN XY: 727222
GnomAD4 genome ? AF: 0.000262 AC: 40AN: 152382Hom.: 0 Cov.: 32 AF XY: 0.000309 AC XY: 23AN XY: 74512
ClinVar
Submissions by phenotype
Immunodeficiency 35 Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 01, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at