Variant rs280496 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.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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.94

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
TYK2	NM_003331.5 linkuse as main transcript	c.3200+122G>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.3200+122G>C		intron_variant		1	NM_003331.5	ENSP00000431885	P1

Frequencies

GnomAD3 genomes

AF:

0.288

AC:

43797

AN:

152082

Hom.:

7180

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.286

AC XY:

21284

AN XY:

74416

show subpopulations

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:2

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 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

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