Variant chr19-10379726-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 NM_003331.5(TYK2):c.-132T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 152,152 control chromosomes in the GnomAD database, including 3,251 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3251 hom., cov: 31)

Exomes 𝑓: 0.12 ( 0 hom. )

Consequence

TYK2
NM_003331.5 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.256

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 19-10379726-A-G is Benign according to our data. Variant chr19-10379726-A-G is described in ClinVar as [Benign]. Clinvar id is 327965.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TYK2	NM_003331.5 linkuse as main transcript	c.-132T>C		5_prime_UTR_variant	2/25	ENST00000525621.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TYK2	ENST00000525621.6 linkuse as main transcript	c.-132T>C		5_prime_UTR_variant	2/25	1	NM_003331.5	P1

Frequencies

GnomAD3 genomes

AF:

0.191

AC:

29078

AN:

151904

Hom.:

3240

Cov.:

show subpopulations

Gnomad AFR

AF:

0.300

Gnomad AMI

AF:

0.0932

Gnomad AMR

AF:

0.127

Gnomad ASJ

AF:

0.166

Gnomad EAS

AF:

0.0346

Gnomad SAS

AF:

0.191

Gnomad FIN

AF:

0.186

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.155

Gnomad OTH

AF:

0.175

GnomAD4 exome

AF:

0.115

AC:

AN:

130

Hom.:

Cov.:

AF XY:

0.143

AC XY:

AN XY:

show subpopulations

Gnomad4 EAS exome

AF:

0.0984

Gnomad4 FIN exome

AF:

0.333

Gnomad4 NFE exome

AF:

0.500

GnomAD4 genome

AF:

0.192

AC:

29134

AN:

152022

Hom.:

3251

Cov.:

AF XY:

0.190

AC XY:

14081

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.301

Gnomad4 AMR

AF:

0.127

Gnomad4 ASJ

AF:

0.166

Gnomad4 EAS

AF:

0.0345

Gnomad4 SAS

AF:

0.191

Gnomad4 FIN

AF:

0.186

Gnomad4 NFE

AF:

0.155

Gnomad4 OTH

AF:

0.179

Alfa

AF:

0.161

Hom.:

2912

Bravo

AF:

0.190

Asia WGS

AF:

0.143

AC:

494

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Immunodeficiency 35

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

9.4

DANN

Benign

0.74

Splicing

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