Variant 19-10354011-A-G 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 ENST00000525621.6(TYK2):c.2908+31T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 1,610,030 control chromosomes in the GnomAD database, including 232,452 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.56 ( 23886 hom., cov: 33)

Exomes 𝑓: 0.53 ( 208566 hom. )

Consequence

TYK2
ENST00000525621.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.76

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=-0.82).

BP6

Variant 19-10354011-A-G is Benign according to our data. Variant chr19-10354011-A-G is described in ClinVar as [Benign]. Clinvar id is 673300.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.633 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.2908+31T>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.2908+31T>C		intron_variant		1	NM_003331.5	ENSP00000431885	P1

Frequencies

GnomAD3 genomes

AF:

0.556

AC:

84405

AN:

151810

Hom.:

23842

Cov.:

show subpopulations

Gnomad AFR

AF:

0.639

Gnomad AMI

AF:

0.590

Gnomad AMR

AF:

0.484

Gnomad ASJ

AF:

0.563

Gnomad EAS

AF:

0.636

Gnomad SAS

AF:

0.542

Gnomad FIN

AF:

0.532

Gnomad MID

AF:

0.586

Gnomad NFE

AF:

0.520

Gnomad OTH

AF:

0.530

GnomAD3 exomes

AF:

0.527

AC:

131111

AN:

248602

Hom.:

35246

AF XY:

0.527

AC XY:

71011

AN XY:

134860

show subpopulations

Gnomad AFR exome

AF:

0.640

Gnomad AMR exome

AF:

0.398

Gnomad ASJ exome

AF:

0.551

Gnomad EAS exome

AF:

0.651

Gnomad SAS exome

AF:

0.523

Gnomad FIN exome

AF:

0.537

Gnomad NFE exome

AF:

0.528

Gnomad OTH exome

AF:

0.525

GnomAD4 exome

AF:

0.533

AC:

776476

AN:

1458102

Hom.:

208566

Cov.:

AF XY:

0.531

AC XY:

385216

AN XY:

725498

show subpopulations

Gnomad4 AFR exome

AF:

0.648

Gnomad4 AMR exome

AF:

0.410

Gnomad4 ASJ exome

AF:

0.548

Gnomad4 EAS exome

AF:

0.570

Gnomad4 SAS exome

AF:

0.519

Gnomad4 FIN exome

AF:

0.540

Gnomad4 NFE exome

AF:

0.532

Gnomad4 OTH exome

AF:

0.552

GnomAD4 genome

AF:

0.556

AC:

84508

AN:

151928

Hom.:

23886

Cov.:

AF XY:

0.554

AC XY:

41162

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.640

Gnomad4 AMR

AF:

0.485

Gnomad4 ASJ

AF:

0.563

Gnomad4 EAS

AF:

0.636

Gnomad4 SAS

AF:

0.541

Gnomad4 FIN

AF:

0.532

Gnomad4 NFE

AF:

0.520

Gnomad4 OTH

AF:

0.531

Alfa

AF:

0.489

Hom.:

3951

Bravo

AF:

0.558

Asia WGS

AF:

0.585

AC:

2030

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 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. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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 77% of patients studied by a panel of primary immunodeficiencies. Number of patients: 74. Only high quality variants are reported. -

Immunodeficiency 35

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.35

DANN

Benign

0.27

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.1

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