VCV000987750.3 - ClinVar

NM_005534.4(IFNGR2):c.4del (p.Arg2fs)

Germline

Classification

no assertion criteria provided. Learn more about how ClinVar calculates review status.

Pathogenic

This classification is based on the single submission received

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_005534.4(IFNGR2):c.4del (p.Arg2fs)

Variation ID: 987750 Accession: VCV000987750.3

Type and length

Deletion, 1 bp

Location

Cytogenetic: 21q22.11 21: 33403547 (GRCh38) [ NCBI UCSC ] 21: 34775853 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Oct 10, 2021	Oct 10, 2021	Oct 14, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_005534.4:c.4del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_005525.2:p.Arg2fs	frameshift
NM_001329128.2:c.4del	NP_001316057.1:p.Arg2fs	frameshift
NC_000021.9:g.33403547del
NC_000021.8:g.34775853del
NG_007570.2:g.23555del
LRG_67:g.23555del

... more HGVS ... less HGVS

Protein change

R2fs

Other names

Canonical SPDI

NC_000021.9:33403546:C:

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA1139666835 OMIM: 147569.0006 dbSNP: rs2083655919 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
IFNGR2		-	-	GRCh38 GRCh38 GRCh37	154	345
LOC119266102	-	-	-	GRCh38	-	69

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Immunodeficiency 28	Pathogenic (1)	no assertion criteria provided	Oct 14, 2025	RCV001269033.4

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	Expand all rows Collapse all rows Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Oct 14, 2025) C Contributing to aggregate classification	no assertion criteria provided	IMMUNODEFICIENCY 28	OMIM Accession: SCV001448221.2 First in ClinVar: Dec 07, 2020 Last updated: Oct 10, 2021	Publications: Oleaga-Quintas, C., Deswarte, C., (more...) Oleaga-Quintas, C., Deswarte, C., Moncada-Velez, M., Metin, A., Rao, I. K., Kanik-Yuksek, S., Nieto-Patlan, A., Guerin, A., Gulhan, B., Murthy, S., Ozkaya-Parlakay, A., Abel, L., Martinez-Barricarte, R., Perez de Diego, R., Boisson-Dupuis, S., Kong, X.-F., Casanova, J.-L., Bustamante, J. A purely quantitative form of partial recessive IFN-gamma-R2 deficiency caused by mutations of the initiation or second codon. Hum. Molec. Genet. 27: 3919-3935, 2018. Note: Erratum: Hum. Molec. Genet. 28: 524 only, 2019. Observation: 1 Collection method: literature only Allele origin: germline Affected status: not provided more Observation 1 Collection method: literature only Allele origin: germline Affected status: not provided Comment on evidence: In an Indian boy, born to consanguineous parents, with susceptibility to mycobacterial disease (IMD28; 614889), Oleaga-Quintas et al. (2018) identified a homozygous 1-bp deletion (c.4delC) … (more) In an Indian boy, born to consanguineous parents, with susceptibility to mycobacterial disease (IMD28; 614889), Oleaga-Quintas et al. (2018) identified a homozygous 1-bp deletion (c.4delC) in the IFNGR2 gene, predicted to cause early termination 22 residues downstream of the start codon. The mutation, which was identified by whole-exome sequencing and confirmed by Sanger sequencing, was present in heterozygous state in the parents. The mutation was not present in the gnomAD database. Elevated levels of IFNG (147570) were detected in plasma from the patient compared to controls. Overexpression of the mutant IFNGR2 cDNA in HEK293-T cells resulted in a reduced amount of full-length protein. Expression of IFNGR2 with the c.4delC mutation in SV40F cells resulted in an impaired, but not absent, response to IFNG stimulation. (less)

Citation text

Oleaga-Quintas, C., Deswarte, C., Moncada-Velez, M., Metin, A., Rao, I. K., Kanik-Yuksek, S., Nieto-Patlan, A., Guerin, A., Gulhan, B., Murthy, S., Ozkaya-Parlakay, A., Abel, L., Martinez-Barricarte, R., Perez de Diego, R., Boisson-Dupuis, S., Kong, X.-F., Casanova, J.-L., Bustamante, J. A purely quantitative form of partial recessive IFN-gamma-R2 deficiency caused by mutations of the initiation or second codon. Hum. Molec. Genet. 27: 3919-3935, 2018. Note: Erratum: Hum. Molec. Genet. 28: 524 only, 2019.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Oleaga-Quintas, C., Deswarte, C., Moncada-Velez, M., Metin, A., Rao, I. K., Kanik-Yuksek, S., Nieto-Patlan, A., Guerin, A., Gulhan, B., Murthy, S., Ozkaya-Parlakay, A., Abel, L., Martinez-Barricarte, R., Perez de Diego, R., Boisson-Dupuis, S., Kong, X.-F., Casanova, J.-L., Bustamante, J. A purely quantitative form of partial recessive IFN-gamma-R2 deficiency caused by mutations of the initiation or second codon. Hum. Molec. Genet. 27: 3919-3935, 2018. Note: Erratum: Hum. Molec. Genet. 28: 524 only, 2019.	-	-	-	-

Text-mined citations for rs2083655919 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Oct 18, 2025