NM_001322934.2(NFKB2):c.14A>G (p.Tyr5Cys) AND Immunodeficiency, common variable, 10

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 16, 2024
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:: RCV000817242.9

Allele description [Variation Report for NM_001322934.2(NFKB2):c.14A>G (p.Tyr5Cys)]

NM_001322934.2(NFKB2):c.14A>G (p.Tyr5Cys)

Gene:

NFKB2:nuclear factor kappa B subunit 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q24.32

Genomic location:

Preferred name:

NM_001322934.2(NFKB2):c.14A>G (p.Tyr5Cys)

HGVS:

NC_000010.11:g.102395973A>G
NG_033874.2:g.6864A>G
NM_001077494.3:c.14A>G
NM_001261403.3:c.14A>G
NM_001288724.1:c.14A>G
NM_001322934.2:c.14A>GMANE SELECT
NM_001322935.1:c.14A>G
NM_002502.6:c.14A>G
NP_001070962.1:p.Tyr5Cys
NP_001248332.1:p.Tyr5Cys
NP_001275653.1:p.Tyr5Cys
NP_001309863.1:p.Tyr5Cys
NP_001309864.1:p.Tyr5Cys
NP_002493.3:p.Tyr5Cys
LRG_1347t1:c.14A>G
LRG_1347:g.6864A>G
LRG_1347p1:p.Tyr5Cys
NC_000010.10:g.104155730A>G
NG_033874.1:g.6864A>G

Protein change:

Y5C

Links:

dbSNP: rs200361192

NCBI 1000 Genomes Browser:

rs200361192

Molecular consequence:

NM_001077494.3:c.14A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001261403.3:c.14A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001288724.1:c.14A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322934.2:c.14A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322935.1:c.14A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_002502.6:c.14A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Immunodeficiency, common variable, 10
Synonyms:: IMMUNODEFICIENCY, COMMON VARIABLE, WITH CENTRAL ADRENAL INSUFFICIENCY; DEFICIT IN ANTERIOR PITUITARY FUNCTION AND VARIABLE IMMUNODEFICIENCY
Identifiers:: MONDO: MONDO:0014260; MedGen: C3809991; OMIM: 615577

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000957792	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 16, 2024)	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

SCV000957792

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 16, 2024)

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, SCV000957792.6

#	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 tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 5 of the NFKB2 protein (p.Tyr5Cys). This variant is present in population databases (rs200361192, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with NFKB2-related conditions. ClinVar contains an entry for this variant (Variation ID: 660112). 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. 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: Oct 13, 2024

ClinVar

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