19-10357771-G-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_003331.5(TYK2):c.2459C>A(p.Pro820His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00141 in 1,609,950 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_003331.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TYK2 | NM_003331.5 | c.2459C>A | p.Pro820His | missense_variant | Exon 17 of 25 | ENST00000525621.6 | NP_003322.3 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00792 AC: 1206AN: 152230Hom.: 13 Cov.: 33
GnomAD3 exomes AF: 0.00178 AC: 429AN: 241360Hom.: 6 AF XY: 0.00138 AC XY: 181AN XY: 131258
GnomAD4 exome AF: 0.000729 AC: 1063AN: 1457602Hom.: 12 Cov.: 31 AF XY: 0.000607 AC XY: 440AN XY: 724806
GnomAD4 genome AF: 0.00794 AC: 1210AN: 152348Hom.: 13 Cov.: 33 AF XY: 0.00758 AC XY: 565AN XY: 74510
ClinVar
Submissions by phenotype
Immunodeficiency 35 Benign:2
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. -
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not provided Benign:1
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
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at