NM_001364905.1(LRBA):c.194T>C (p.Ile65Thr) AND Combined immunodeficiency due to LRBA deficiency

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Jan 29, 2024
Review status:: criteria provided, conflicting classifications

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:: RCV000768012.13

Allele description [Variation Report for NM_001364905.1(LRBA):c.194T>C (p.Ile65Thr)]

NM_001364905.1(LRBA):c.194T>C (p.Ile65Thr)

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.194T>C (p.Ile65Thr)

HGVS:

NC_000004.12:g.151014449A>G
NG_032855.1:g.6049T>C
NM_001199282.2:c.194T>C
NM_001364905.1:c.194T>CMANE SELECT
NM_001367550.1:c.194T>C
NM_006726.4:c.194T>C
NP_001186211.2:p.Ile65Thr
NP_001351834.1:p.Ile65Thr
NP_001354479.1:p.Ile65Thr
NP_006717.2:p.Ile65Thr
LRG_1324t1:c.194T>C
LRG_1324:g.6049T>C
LRG_1324p1:p.Ile65Thr
NC_000004.11:g.151935601A>G

Protein change:

I65T

Links:

dbSNP: rs148385798

NCBI 1000 Genomes Browser:

rs148385798

Molecular consequence:

NM_001199282.2:c.194T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001364905.1:c.194T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001367550.1:c.194T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_006726.4:c.194T>C - 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
SCV000898804	Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 30, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001107515	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Benign (Jan 29, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001525230	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jul 2, 2019)	unknown	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

SCV000898804

Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Mar 30, 2021)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV001107515

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Benign
(Jan 29, 2024)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV001525230

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jul 2, 2019)

unknown

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
not provided	unknown	yes	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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago, SCV000898804.2

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

Description

LRBA NM_006726.4 exon 2 p.Ile65Thr (c.194T>C): This variant has not been reported in the literature but is present in 0.7% (169/24028) of African alleles, including 1 homozygote, in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs148385798). Evolutionary conservation and computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.

#	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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001107515.6

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

#	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

From Baylor Genetics, SCV001525230.1

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

Description

This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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