NM_003331.5(TYK2):c.1787G>C (p.Gly596Ala) AND Immunodeficiency 35

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 2, 2022
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:: RCV002871359.2

Allele description [Variation Report for NM_003331.5(TYK2):c.1787G>C (p.Gly596Ala)]

NM_003331.5(TYK2):c.1787G>C (p.Gly596Ala)

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.1787G>C (p.Gly596Ala)

HGVS:

NC_000019.10:g.10361942C>G
NG_007872.1:g.23631G>C
NM_001385197.1:c.1787G>C
NM_001385198.1:c.1787G>C
NM_001385199.1:c.1773+136G>C
NM_001385200.1:c.1787G>C
NM_001385201.1:c.1589G>C
NM_001385202.1:c.1787G>C
NM_001385203.1:c.1787G>C
NM_001385204.1:c.1787G>C
NM_001385205.1:c.1697G>C
NM_001385206.1:c.1661G>C
NM_001385207.1:c.1774-5G>C
NM_001406461.1:c.1787G>C
NM_003331.5:c.1787G>CMANE SELECT
NP_001372126.1:p.Gly596Ala
NP_001372127.1:p.Gly596Ala
NP_001372129.1:p.Gly596Ala
NP_001372130.1:p.Gly530Ala
NP_001372131.1:p.Gly596Ala
NP_001372132.1:p.Gly596Ala
NP_001372133.1:p.Gly596Ala
NP_001372134.1:p.Gly566Ala
NP_001372135.1:p.Gly554Ala
NP_001393390.1:p.Gly596Ala
NP_003322.3:p.Gly596Ala
NP_003322.3:p.Gly596Ala
LRG_121t1:c.1787G>C
LRG_121:g.23631G>C
LRG_121p1:p.Gly596Ala
NC_000019.9:g.10472618C>G
NM_003331.4:c.1787G>C

Protein change:

G530A

Molecular consequence:

NM_001385199.1:c.1773+136G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001385207.1:c.1774-5G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001385197.1:c.1787G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001385198.1:c.1787G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001385200.1:c.1787G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001385201.1:c.1589G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001385202.1:c.1787G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001385203.1:c.1787G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001385204.1:c.1787G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001385205.1:c.1697G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001385206.1:c.1661G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001406461.1:c.1787G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_003331.5:c.1787G>C - 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
SCV003230472	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 2, 2022)	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

SCV003230472

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 2, 2022)

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003230472.1

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

Description

This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 596 of the TYK2 protein (p.Gly596Ala). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TYK2-related conditions. 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: "Probably Damaging"; Align-GVGD: "Not Available"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.

#	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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