NM_003331.5(TYK2):c.2920_2941del (p.Leu974fs) AND Immunodeficiency 35

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 12, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003515798.2

Allele description [Variation Report for NM_003331.5(TYK2):c.2920_2941del (p.Leu974fs)]

NM_003331.5(TYK2):c.2920_2941del (p.Leu974fs)

Gene:

TYK2:tyrosine kinase 2 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

19p13.2

Genomic location:

Preferred name:

NM_003331.5(TYK2):c.2920_2941del (p.Leu974fs)

HGVS:

NC_000019.10:g.10353616_10353637del
NG_007872.1:g.31938_31959del
NG_140359.1:g.470_491del
NM_001385197.1:c.2920_2941del
NM_001385198.1:c.2920_2941del
NM_001385199.1:c.2734_2755del
NM_001385200.1:c.2917_2938del
NM_001385201.1:c.2722_2743del
NM_001385202.1:c.2836_2857del
NM_001385203.1:c.3001_3022del
NM_001385204.1:c.3130_3151del
NM_001385205.1:c.2830_2851del
NM_001385206.1:c.2794_2815del
NM_001385207.1:c.2902_2923del
NM_001406461.1:c.2920_2941del
NM_003331.5:c.2920_2941delMANE SELECT
NP_001372126.1:p.Leu974fs
NP_001372127.1:p.Leu974fs
NP_001372128.1:p.Leu912fs
NP_001372129.1:p.Leu973fs
NP_001372130.1:p.Leu908fs
NP_001372131.1:p.Leu946fs
NP_001372132.1:p.Leu1001fs
NP_001372133.1:p.Leu1044fs
NP_001372134.1:p.Leu944fs
NP_001372135.1:p.Leu932fs
NP_001372136.1:p.Leu968fs
NP_001393390.1:p.Leu974fs
NP_003322.3:p.Leu974Cysfs
NP_003322.3:p.Leu974fs
LRG_121t1:c.2918_2939del22
LRG_121:g.31938_31959del
LRG_121p1:p.Leu974Cysfs
NC_000019.9:g.10464290_10464311del
NC_000019.9:g.10464292_10464313del
NM_003331.4:c.2918_2939del22

Protein change:

L1001fs

Molecular consequence:

NM_001385197.1:c.2920_2941del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001385198.1:c.2920_2941del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001385199.1:c.2734_2755del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001385200.1:c.2917_2938del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001385201.1:c.2722_2743del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001385202.1:c.2836_2857del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001385203.1:c.3001_3022del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001385204.1:c.3130_3151del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001385205.1:c.2830_2851del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001385206.1:c.2794_2815del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001385207.1:c.2902_2923del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406461.1:c.2920_2941del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_003331.5:c.2920_2941del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Immunodeficiency 35 (IMD35)
Synonyms:: HIES WITH ATYPICAL MYCOBACTERIOSIS, AUTOSOMAL RECESSIVE; HYPER-IgE SYNDROME WITH ATYPICAL MYCOBACTERIOSIS, AUTOSOMAL RECESSIVE; TYK2 DEFICIENCY; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0012682; MedGen: C1969086; OMIM: 611521

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Plant sample from Ozomelis stauropetala
Plant sample from Ozomelis stauropetala

biosample
Eurotiales beta-tubulin gene, partial cds.
Eurotiales beta-tubulin gene, partial cds.
PopSet: 1697170535

PopSet
RNAseq_dysgenic_rep2
RNAseq_dysgenic_rep2

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004325117	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 12, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 22402565, 26304966, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004325117

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 12, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A patient with tyrosine kinase 2 deficiency without hyper-IgE syndrome.

Kilic SS, Hacimustafaoglu M, Boisson-Dupuis S, Kreins AY, Grant AV, Abel L, Casanova JL.

J Pediatr. 2012 Jun;160(6):1055-7. doi: 10.1016/j.jpeds.2012.01.056. Epub 2012 Mar 7. Erratum in: J Pediatr. 2012 Nov;161(5):974. J Pediatr. 2013 Mar;162(3):658.

PubMed [citation]

PMID:: 22402565
PMCID:: PMC3360808

Human TYK2 deficiency: Mycobacterial and viral infections without hyper-IgE syndrome.

Kreins AY, Ciancanelli MJ, Okada S, Kong XF, Ramírez-Alejo N, Kilic SS, El Baghdadi J, Nonoyama S, Mahdaviani SA, Ailal F, Bousfiha A, Mansouri D, Nievas E, Ma CS, Rao G, Bernasconi A, Sun Kuehn H, Niemela J, Stoddard J, Deveau P, Cobat A, El Azbaoui S, et al.

J Exp Med. 2015 Sep 21;212(10):1641-62. doi: 10.1084/jem.20140280. Epub 2015 Aug 24.

PubMed [citation]

PMID:: 26304966
PMCID:: PMC4577846

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004325117.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with TYK2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu974Cysfs*44) in the TYK2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TYK2 are known to be pathogenic (PMID: 22402565, 26304966).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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