rs12720355

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_003331.5(TYK2):c.1953C>T(p.Ile651Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0136 in 1,612,786 control chromosomes in the GnomAD database, including 179 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 17 hom., cov: 31)

Exomes 𝑓: 0.014 ( 162 hom. )

Consequence

TYK2
NM_003331.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -2.44

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 19-10361776-G-A is Benign according to our data. Variant chr19-10361776-G-A is described in ClinVar as [Benign]. Clinvar id is 259042.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-10361776-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.44 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00999 (1514/151540) while in subpopulation NFE AF= 0.0159 (1077/67864). AF 95% confidence interval is 0.0151. There are 17 homozygotes in gnomad4. There are 730 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TYK2	NM_003331.5 link	c.1953C>T	p.Ile651Ile	synonymous_variant	Exon 13 of 25	ENST00000525621.6	NP_003322.3	P29597A0A024R7E4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TYK2	ENST00000525621.6 link	c.1953C>T	p.Ile651Ile	synonymous_variant	Exon 13 of 25	1	NM_003331.5	ENSP00000431885.1		P29597

Frequencies

GnomAD3 genomes

AF:

0.0100

AC:

1514

AN:

151418

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00250

Gnomad AMI

AF:

0.0287

Gnomad AMR

AF:

0.00737

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.00751

Gnomad FIN

AF:

0.0125

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.0159

Gnomad OTH

AF:

0.00719

GnomAD3 exomes

AF:

0.00957

AC:

2398

AN:

250616

Hom.:

AF XY:

0.00984

AC XY:

1334

AN XY:

135576

show subpopulations

Gnomad AFR exome

AF:

0.00265

Gnomad AMR exome

AF:

0.00492

Gnomad ASJ exome

AF:

0.00427

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00666

Gnomad FIN exome

AF:

0.0123

Gnomad NFE exome

AF:

0.0142

Gnomad OTH exome

AF:

0.0104

GnomAD4 exome

AF:

0.0140

AC:

20398

AN:

1461246

Hom.:

162

Cov.:

AF XY:

0.0139

AC XY:

10091

AN XY:

726978

show subpopulations

Gnomad4 AFR exome

AF:

0.00221

Gnomad4 AMR exome

AF:

0.00543

Gnomad4 ASJ exome

AF:

0.00413

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00663

Gnomad4 FIN exome

AF:

0.0118

Gnomad4 NFE exome

AF:

0.0162

Gnomad4 OTH exome

AF:

0.0116

GnomAD4 genome

AF:

0.00999

AC:

1514

AN:

151540

Hom.:

Cov.:

AF XY:

0.00986

AC XY:

730

AN XY:

74058

show subpopulations

Gnomad4 AFR

AF:

0.00250

Gnomad4 AMR

AF:

0.00736

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.000196

Gnomad4 SAS

AF:

0.00751

Gnomad4 FIN

AF:

0.0125

Gnomad4 NFE

AF:

0.0159

Gnomad4 OTH

AF:

0.00712

Alfa

AF:

0.0133

Hom.:

Bravo

AF:

0.00936

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.0145

EpiControl

AF:

0.0132

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Apr 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TYK2: BP4, BP7, BS1, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Immunodeficiency 35

Benign:2

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.8

DANN

Benign

0.63

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