NM_001322934.2(NFKB2):c.361G>A (p.Ala121Thr) AND Immunodeficiency, common variable, 10

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 19, 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:: RCV003583472.2

Allele description [Variation Report for NM_001322934.2(NFKB2):c.361G>A (p.Ala121Thr)]

NM_001322934.2(NFKB2):c.361G>A (p.Ala121Thr)

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.361G>A (p.Ala121Thr)

HGVS:

NC_000010.11:g.102397021G>A
NG_033874.2:g.7912G>A
NM_001077493.1:c.361G>A
NM_001077494.3:c.361G>A
NM_001261403.3:c.361G>A
NM_001288724.1:c.361G>A
NM_001322934.2:c.361G>AMANE SELECT
NM_001322935.1:c.361G>A
NM_002502.6:c.361G>A
NP_001070961.1:p.Ala121Thr
NP_001070962.1:p.Ala121Thr
NP_001248332.1:p.Ala121Thr
NP_001275653.1:p.Ala121Thr
NP_001309863.1:p.Ala121Thr
NP_001309864.1:p.Ala121Thr
NP_002493.3:p.Ala121Thr
LRG_1347t1:c.361G>A
LRG_1347:g.7912G>A
LRG_1347p1:p.Ala121Thr
NC_000010.10:g.104156778G>A
NR_048560.1:n.924G>A

Protein change:

A121T

Molecular consequence:

NM_001077493.1:c.361G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001077494.3:c.361G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001261403.3:c.361G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001288724.1:c.361G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322934.2:c.361G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322935.1:c.361G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_002502.6:c.361G>A - 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
SCV004277133	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 19, 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

SCV004277133

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 19, 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, SCV004277133.1

#	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 alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 121 of the NFKB2 protein (p.Ala121Thr). This variant is present in population databases (rs781738940, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with NFKB2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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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