rs8108236

Positions:

• chr19-10355156-G-A

Variant summary

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

The NM_003331.5(TYK2):​c.2618-547C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0921 in 152,090 control chromosomes in the GnomAD database, including 685 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 0.092 (685 hom., cov: 31)
• Consequence: TYK2 NM_003331.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.865

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TYK2	NM_003331.5	c.2618-547C>T		intron_variant		ENST00000525621.6	NP_003322.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TYK2	ENST00000525621.6	c.2618-547C>T		intron_variant		1	NM_003331.5	ENSP00000431885	P1

Frequencies

GnomAD3 genomes AF: 0.0920 AC: 13986 AN: 151972 Hom.: 685 Cov.: 31

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0687

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.0125

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.0881

Gnomad OTH AF: 0.101

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0921 AC: 14005 AN: 152090 Hom.: 685 Cov.: 31 AF XY: 0.0923 AC XY: 6864 AN XY: 74352

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.0685

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.0123

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.0881

Gnomad4 OTH AF: 0.0998

Alfa AF: 0.0913 Hom.: 820

Bravo AF: 0.0893

Asia WGS AF: 0.0840 AC: 292 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.9
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs8108236; hg19: chr19-10465832;