NM_001079.4(ZAP70):c.1555C>T (p.Arg519Cys) AND ZAP70-Related Severe Combined Immunodeficiency

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 11, 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:: RCV003583557.2

Allele description [Variation Report for NM_001079.4(ZAP70):c.1555C>T (p.Arg519Cys)]

NM_001079.4(ZAP70):c.1555C>T (p.Arg519Cys)

Gene:

ZAP70:zeta chain of T cell receptor associated protein kinase 70 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q11.2

Genomic location:

Preferred name:

NM_001079.4(ZAP70):c.1555C>T (p.Arg519Cys)

HGVS:

NC_000002.12:g.97737829C>T
NG_007727.1:g.29262C>T
NM_001079.4:c.1555C>TMANE SELECT
NM_001378594.1:c.1555C>T
NM_207519.2:c.634C>T
NP_001070.2:p.Arg519Cys
NP_001070.2:p.Arg519Cys
NP_001365523.1:p.Arg519Cys
NP_997402.1:p.Arg212Cys
LRG_126t1:c.1555C>T
LRG_126:g.29262C>T
LRG_126p1:p.Arg519Cys
NC_000002.11:g.98354292C>T
NM_001079.3:c.1555C>T

Protein change:

R212C

Molecular consequence:

NM_001079.4:c.1555C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001378594.1:c.1555C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_207519.2:c.634C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: ZAP70-Related Severe Combined Immunodeficiency
Identifiers:: MedGen: C2931299

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004344450	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 11, 2023)	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

SCV004344450

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 11, 2023)

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, SCV004344450.1

#	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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant has not been reported in the literature in individuals affected with ZAP70-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 519 of the ZAP70 protein (p.Arg519Cys).

#	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

ClinVar

Relating variation to medicine