Variant rs34725611 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.629+26T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 1,604,892 control chromosomes in the GnomAD database, including 65,031 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4868 hom., cov: 31)

Exomes 𝑓: 0.28 ( 60163 hom. )

Consequence

TYK2
NM_003331.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.15

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=-0.88).

BP6

Variant 19-10366391-A-G is Benign according to our data. Variant chr19-10366391-A-G is described in ClinVar as [Benign]. Clinvar id is 1243741.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.498 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.629+26T>C		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.629+26T>C		intron_variant		1	NM_003331.5	ENSP00000431885	P1

Frequencies

GnomAD3 genomes

AF:

0.235

AC:

35563

AN:

151644

Hom.:

4863

Cov.:

show subpopulations

Gnomad AFR

AF:

0.110

Gnomad AMI

AF:

0.416

Gnomad AMR

AF:

0.226

Gnomad ASJ

AF:

0.325

Gnomad EAS

AF:

0.514

Gnomad SAS

AF:

0.287

Gnomad FIN

AF:

0.238

Gnomad MID

AF:

0.280

Gnomad NFE

AF:

0.279

Gnomad OTH

AF:

0.247

GnomAD3 exomes

AF:

0.277

AC:

68949

AN:

248766

Hom.:

10632

AF XY:

0.280

AC XY:

37664

AN XY:

134478

show subpopulations

Gnomad AFR exome

AF:

0.110

Gnomad AMR exome

AF:

0.199

Gnomad ASJ exome

AF:

0.308

Gnomad EAS exome

AF:

0.536

Gnomad SAS exome

AF:

0.279

Gnomad FIN exome

AF:

0.243

Gnomad NFE exome

AF:

0.286

Gnomad OTH exome

AF:

0.281

GnomAD4 exome

AF:

0.282

AC:

410458

AN:

1453174

Hom.:

60163

Cov.:

AF XY:

0.282

AC XY:

203785

AN XY:

721412

show subpopulations

Gnomad4 AFR exome

AF:

0.103

Gnomad4 AMR exome

AF:

0.204

Gnomad4 ASJ exome

AF:

0.308

Gnomad4 EAS exome

AF:

0.445

Gnomad4 SAS exome

AF:

0.276

Gnomad4 FIN exome

AF:

0.250

Gnomad4 NFE exome

AF:

0.286

Gnomad4 OTH exome

AF:

0.292

GnomAD4 genome

AF:

0.234

AC:

35577

AN:

151718

Hom.:

4868

Cov.:

AF XY:

0.234

AC XY:

17315

AN XY:

74102

show subpopulations

Gnomad4 AFR

AF:

0.111

Gnomad4 AMR

AF:

0.227

Gnomad4 ASJ

AF:

0.325

Gnomad4 EAS

AF:

0.514

Gnomad4 SAS

AF:

0.287

Gnomad4 FIN

AF:

0.238

Gnomad4 NFE

AF:

0.279

Gnomad4 OTH

AF:

0.246

Alfa

AF:

0.257

Hom.:

1022

Bravo

AF:

0.232

Asia WGS

AF:

0.355

AC:

1230

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	Jun 26, 2018	- -

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 36% of patients studied by a panel of primary immunodeficiencies. Number of patients: 35. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.65

DANN

Benign

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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