rs280496

chr19-10352804-C-Gchr19-10352804-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003331.5(TYK2):c.3200+122G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 1,324,388 control chromosomes in the GnomAD database, including 43,067 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.29 (7209 hom., cov: 32)
  • Exomes 𝑓: 0.24 (35858 hom.)
• Consequence: TYK2 NM_003331.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.94

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 19-10352804-C-G is Benign according to our data. Variant chr19-10352804-C-G is described in ClinVar as [Benign]. Clinvar id is 673301.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TYK2	NM_003331.5	c.3200+122G>C		intron_variant		ENST00000525621.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TYK2	ENST00000525621.6	c.3200+122G>C		intron_variant		1	NM_003331.5	P1

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43797 AN: 152082 Hom.: 7180 Cov.: 32

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.0861

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.269

GnomAD4 exome AF: 0.241 AC: 282894 AN: 1172188 Hom.: 35858 AF XY: 0.241 AC XY: 139260 AN XY: 578128

Gnomad4 AFR exome AF: 0.461

Gnomad4 AMR exome AF: 0.137

Gnomad4 ASJ exome AF: 0.239

Gnomad4 EAS exome AF: 0.0844

Gnomad4 SAS exome AF: 0.249

Gnomad4 FIN exome AF: 0.279

Gnomad4 NFE exome AF: 0.242

Gnomad4 OTH exome AF: 0.251

GnomAD4 genome AF: 0.288 AC: 43876 AN: 152200 Hom.: 7209 Cov.: 32 AF XY: 0.286 AC XY: 21284 AN XY: 74416

Gnomad4 AFR AF: 0.447

Gnomad4 AMR AF: 0.188

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.0852

Gnomad4 SAS AF: 0.257

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.236

Gnomad4 OTH AF: 0.272

Alfa AF: 0.115 Hom.: 174

Bravo AF: 0.287

Asia WGS AF: 0.228 AC: 791 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2018

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: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.77
Dann	Benign	0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs280496; hg19: chr19-10463480; COSMIC: COSV53385827; COSMIC: COSV53385827;