NM_001364905.1(LRBA):c.8441G>A (p.Arg2814Gln) AND Combined immunodeficiency due to LRBA deficiency

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 3, 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:: RCV000804307.5

Allele description

NM_001364905.1(LRBA):c.8441G>A (p.Arg2814Gln)

Gene:

LRBA:LPS responsive beige-like anchor protein [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4q31.3

Genomic location:

Preferred name:

NM_001364905.1(LRBA):c.8441G>A (p.Arg2814Gln)

HGVS:

NC_000004.12:g.150277880C>T
NG_032855.1:g.742618G>A
NM_001199282.2:c.8438G>A
NM_001364905.1:c.8441G>AMANE SELECT
NM_001367550.1:c.8456G>A
NM_006726.4:c.8474G>A
NP_001186211.2:p.Arg2813Gln
NP_001351834.1:p.Arg2814Gln
NP_001354479.1:p.Arg2819Gln
NP_006717.2:p.Arg2825Gln
LRG_1324t1:c.8441G>A
LRG_1324:g.742618G>A
LRG_1324p1:p.Arg2814Gln
NC_000004.11:g.151199032C>T

Protein change:

R2813Q

Links:

dbSNP: rs746707676

NCBI 1000 Genomes Browser:

rs746707676

Molecular consequence:

NM_001199282.2:c.8438G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001364905.1:c.8441G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001367550.1:c.8456G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_006726.4:c.8474G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Combined immunodeficiency due to LRBA deficiency
Synonyms:: Common variable immunodeficiency 8, with autoimmunity
Identifiers:: MONDO: MONDO:0013863; MedGen: C3553512; Orphanet: 445018; OMIM: 614700

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000944210	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 3, 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

SCV000944210

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 3, 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 Invitae, SCV000944210.3

#	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 arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 2825 of the LRBA protein (p.Arg2825Gln). This variant is present in population databases (rs746707676, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with LRBA-related conditions. ClinVar contains an entry for this variant (Variation ID: 649387). 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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: May 1, 2024

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