rs280501

Positions:

• chr19-10380646-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The variant allele was found at a frequency of 0.199 in 151,158 control chromosomes in the GnomAD database, including 3,549 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.20 (3549 hom., cov: 31)
  • Exomes 𝑓: 0.075 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: intergenic_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36

Genes affected

(HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.10380646C>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TYK2	ENST00000699360.1	c.-452G>A		upstream_gene_variant				ENSP00000514331.1
TYK2	ENST00000525976.6	c.-452G>A		upstream_gene_variant		3		ENSP00000434831.2
TYK2	ENST00000527481.3	n.-452G>A		upstream_gene_variant		3		ENSP00000466340.2

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30043 AN: 151050 Hom.: 3533 Cov.: 31

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.0938

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.0380

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.184

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0747 AC: 13 AN: 174 Hom.: 0 Cov.: 0 AF XY: 0.0849 AC XY: 9 AN XY: 106

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.0847

Gnomad4 SAS exome AF: 0.0500

Gnomad4 NFE exome AF: 0.0625

GnomAD4 genome AF: 0.199 AC: 30102 AN: 151158 Hom.: 3549 Cov.: 31 AF XY: 0.197 AC XY: 14510 AN XY: 73770

Gnomad4 AFR AF: 0.328

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.0379

Gnomad4 SAS AF: 0.188

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.188

Alfa AF: 0.162 Hom.: 2759

Bravo AF: 0.199

Asia WGS AF: 0.139 AC: 480 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.2
DANN	Benign	0.68

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs280501; hg19: chr19-10491322; COSMIC: COSV53385847; COSMIC: COSV53385847;