NM_003331.5(TYK2):c.286G>T (p.Asp96Tyr) AND Immunodeficiency 35

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 18, 2021
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:: RCV001977894.5

Allele description [Variation Report for NM_003331.5(TYK2):c.286G>T (p.Asp96Tyr)]

NM_003331.5(TYK2):c.286G>T (p.Asp96Tyr)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

19p13.2

Genomic location:

Preferred name:

NM_003331.5(TYK2):c.286G>T (p.Asp96Tyr)

HGVS:

NC_000019.10:g.10368326C>A
NG_007872.1:g.17247G>T
NM_001385197.1:c.286G>T
NM_001385198.1:c.286G>T
NM_001385199.1:c.286G>T
NM_001385200.1:c.286G>T
NM_001385201.1:c.286G>T
NM_001385202.1:c.286G>T
NM_001385203.1:c.286G>T
NM_001385204.1:c.286G>T
NM_001385205.1:c.286G>T
NM_001385206.1:c.286G>T
NM_001385207.1:c.286G>T
NM_003331.5:c.286G>TMANE SELECT
NP_001372126.1:p.Asp96Tyr
NP_001372127.1:p.Asp96Tyr
NP_001372128.1:p.Asp96Tyr
NP_001372129.1:p.Asp96Tyr
NP_001372130.1:p.Asp96Tyr
NP_001372131.1:p.Asp96Tyr
NP_001372132.1:p.Asp96Tyr
NP_001372133.1:p.Asp96Tyr
NP_001372134.1:p.Asp96Tyr
NP_001372135.1:p.Asp96Tyr
NP_001372136.1:p.Asp96Tyr
NP_003322.3:p.Asp96Tyr
LRG_121:g.17247G>T
NC_000019.9:g.10479002C>A

Protein change:

D96Y

Links:

dbSNP: rs2145275479

NCBI 1000 Genomes Browser:

rs2145275479

Molecular consequence:

NM_001385197.1:c.286G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001385198.1:c.286G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001385199.1:c.286G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001385200.1:c.286G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001385201.1:c.286G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001385202.1:c.286G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001385203.1:c.286G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001385204.1:c.286G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001385205.1:c.286G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001385206.1:c.286G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001385207.1:c.286G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_003331.5:c.286G>T - missense variant - [Sequence Ontology: SO:0001583]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002261901	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 18, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002261901

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 18, 2021)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV002261901.3

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Not Available"). This variant has not been reported in the literature in individuals affected with TYK2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces aspartic acid with tyrosine at codon 96 of the TYK2 protein (p.Asp96Tyr). The aspartic acid residue is highly conserved and there is a large physicochemical difference between aspartic acid and tyrosine.

#	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: Mar 5, 2024

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