Variant rs12720270 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003331.5(TYK2):c.1012-36C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 1,565,406 control chromosomes in the GnomAD database, including 31,415 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2637 hom., cov: 33)

Exomes 𝑓: 0.19 ( 28778 hom. )

Consequence

TYK2
NM_003331.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0140

Variant links:

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]

TYK2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 19-10365084-G-A is Benign according to our data. Variant chr19-10365084-G-A is described in ClinVar as [Benign]. Clinvar id is 1257593.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TYK2	NM_003331.5 linkuse as main transcript	c.1012-36C>T		intron_variant		ENST00000525621.6	NP_003322.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TYK2	ENST00000525621.6 linkuse as main transcript	c.1012-36C>T		intron_variant		1	NM_003331.5	ENSP00000431885	P1

Frequencies

GnomAD3 genomes

AF:

0.165

AC:

25031

AN:

152132

Hom.:

2636

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0654

Gnomad AMI

AF:

0.366

Gnomad AMR

AF:

0.166

Gnomad ASJ

AF:

0.224

Gnomad EAS

AF:

0.489

Gnomad SAS

AF:

0.228

Gnomad FIN

AF:

0.151

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.191

Gnomad OTH

AF:

0.174

GnomAD3 exomes

AF:

0.209

AC:

42480

AN:

203320

Hom.:

5284

AF XY:

0.211

AC XY:

22981

AN XY:

108938

show subpopulations

Gnomad AFR exome

AF:

0.0629

Gnomad AMR exome

AF:

0.163

Gnomad ASJ exome

AF:

0.210

Gnomad EAS exome

AF:

0.505

Gnomad SAS exome

AF:

0.224

Gnomad FIN exome

AF:

0.161

Gnomad NFE exome

AF:

0.197

Gnomad OTH exome

AF:

0.201

GnomAD4 exome

AF:

0.194

AC:

274774

AN:

1413156

Hom.:

28778

Cov.:

AF XY:

0.195

AC XY:

136131

AN XY:

698046

show subpopulations

Gnomad4 AFR exome

AF:

0.0578

Gnomad4 AMR exome

AF:

0.161

Gnomad4 ASJ exome

AF:

0.205

Gnomad4 EAS exome

AF:

0.422

Gnomad4 SAS exome

AF:

0.216

Gnomad4 FIN exome

AF:

0.165

Gnomad4 NFE exome

AF:

0.191

Gnomad4 OTH exome

AF:

0.204

GnomAD4 genome

AF:

0.164

AC:

25043

AN:

152250

Hom.:

2637

Cov.:

AF XY:

0.165

AC XY:

12244

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0654

Gnomad4 AMR

AF:

0.167

Gnomad4 ASJ

AF:

0.224

Gnomad4 EAS

AF:

0.490

Gnomad4 SAS

AF:

0.229

Gnomad4 FIN

AF:

0.151

Gnomad4 NFE

AF:

0.191

Gnomad4 OTH

AF:

0.173

Alfa

AF:

0.163

Hom.:

491

Bravo

AF:

0.164

Asia WGS

AF:

0.316

AC:

1094

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 07, 2018	This variant is associated with the following publications: (PMID: 19567624, 31961910) -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 31% of patients studied by a panel of primary immunodeficiencies. Number of patients: 30. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.2

DANN

Benign

0.44

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over