21-33436888-GAT-AAC

Variant names:

• chr21-33436888-GAT-AAC
• NM_005534.4:c.940_942delGATinsAAC
• IFNGR2 p.Asp314Asn

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_005534.4(IFNGR2):​c.940_942delGATinsAAC​(p.Asp314Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IFNGR2 NM_005534.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.04
• Publications: 0 publications found

Genes affected

IFNGR2 (HGNC:5440): (interferon gamma receptor 2) This gene (IFNGR2) encodes the non-ligand-binding beta chain of the gamma interferon receptor. Human interferon-gamma receptor is a heterodimer of IFNGR1 and IFNGR2. Defects in IFNGR2 are a cause of mendelian susceptibility to mycobacterial disease (MSMD), also known as familial disseminated atypical mycobacterial infection. MSMD is a genetically heterogeneous disease with autosomal recessive, autosomal dominant or X-linked inheritance. [provided by RefSeq, Jul 2008]

TMEM50B (HGNC:1280): (transmembrane protein 50B) Predicted to be involved in late endosome to vacuole transport via multivesicular body sorting pathway. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005534.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNGR2	NM_005534.4	MANE Select	c.940_942delGATinsAAC	p.Asp314Asn	missense	N/A	NP_005525.2
	IFNGR2	NM_001329128.2		c.997_999delGATinsAAC	p.Asp333Asn	missense	N/A	NP_001316057.1	E7EUY1
	TMEM50B	NR_040016.2		n.2775+2324_2775+2326delATCinsGTT		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNGR2	ENST00000290219.11	TSL:1 MANE Select	c.940_942delGATinsAAC	p.Asp314Asn	missense	N/A	ENSP00000290219.5	P38484
	TMEM50B	ENST00000420455.5	TSL:1	n.*2120+2324_*2120+2326delATCinsGTT		intron	N/A	ENSP00000397773.1	P56557
	IFNGR2	ENST00000964420.1		c.1090_1092delGATinsAAC	p.Asp364Asn	missense	N/A	ENSP00000634479.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr21-34809195;