NM_005535.3(IL12RB1):c.1877G>A (p.Gly626Asp) AND Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 deficiency

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 18, 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:: RCV003826379.2

Allele description [Variation Report for NM_005535.3(IL12RB1):c.1877G>A (p.Gly626Asp)]

NM_005535.3(IL12RB1):c.1877G>A (p.Gly626Asp)

Gene:

IL12RB1:interleukin 12 receptor subunit beta 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

19p13.11

Genomic location:

Preferred name:

NM_005535.3(IL12RB1):c.1877G>A (p.Gly626Asp)

HGVS:

NC_000019.10:g.18060000C>T
NG_007366.2:g.43950G>A
NM_001290023.2:c.1877G>A
NM_001290024.1:c.1997G>A
NM_005535.3:c.1877G>AMANE SELECT
NP_001276952.1:p.Gly626Asp
NP_001276953.1:p.Gly666Asp
NP_005526.1:p.Gly626Asp
NP_005526.1:p.Gly626Asp
LRG_72t1:c.1877G>A
LRG_72:g.43950G>A
LRG_72p1:p.Gly626Asp
NC_000019.9:g.18170810C>T
NM_005535.1:c.1877G>A

Protein change:

G626D

Molecular consequence:

NM_001290023.2:c.1877G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001290024.1:c.1997G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_005535.3:c.1877G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 deficiency
Synonyms:: IL12RB1 DEFICIENCY; Immunodeficiency 30
Identifiers:: MONDO: MONDO:0013955; MedGen: C4013949; Orphanet: 319552; OMIM: 614891

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004625702	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 18, 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

SCV004625702

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 18, 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, SCV004625702.1

#	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 glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 626 of the IL12RB1 protein (p.Gly626Asp). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with IL12RB1-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 aspartic acid 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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