21-33262573-GCT-AGC

Variant names:

• chr21-33262573-GCT-AGC
• ENST00000382264.7:c.853_855delGCTinsAGC
• IFNAR2 p.Ala285Ser

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

The NM_001385054.1(IFNAR2):​c.722_724delGCTinsAGC​(p.ArgTer241GlnGlnext*?) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. 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.

• Frequency: Genomes: not found (cov: 30)
• Consequence: IFNAR2 NM_001385054.1 stop_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.773
• Publications: 0 publications found

Genes affected

IFNAR2 (HGNC:5433): (interferon alpha and beta receptor subunit 2) The protein encoded by this gene is a type I membrane protein that forms one of the two chains of a receptor for interferons alpha and beta. Binding and activation of the receptor stimulates Janus protein kinases, which in turn phosphorylate several proteins, including STAT1 and STAT2. The protein belongs to the type II cytokine receptor family. Mutations in this gene are associated with Immunodeficiency 45. [provided by RefSeq, Jul 2020]

IFNAR2 Gene-Disease associations (from GenCC):

• immunodeficiency 45

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

IFNAR2-IL10RB (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM4: Stoplost variant in NM_001385054.1 Downstream stopcodon found after 346 codons.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385054.1. 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
	IFNAR2	NM_001289125.3	MANE Select	c.841-220_841-218delGCTinsAGC		intron	N/A	NP_001276054.1	P48551-1
	IFNAR2	NM_001385054.1		c.722_724delGCTinsAGC	p.ArgTer241GlnGlnext*?	stop_lost	N/A	NP_001371983.1
	IFNAR2	NM_000874.5		c.853_855delGCTinsAGC	p.Ala285Ser	missense	N/A	NP_000865.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNAR2	ENST00000382264.7	TSL:1	c.853_855delGCTinsAGC	p.Ala285Ser	missense	N/A	ENSP00000371699.3	P48551-2
	IFNAR2	ENST00000404220.7	TSL:1	c.853_855delGCTinsAGC	p.Ala285Ser	missense	N/A	ENSP00000384309.2	P48551-2
	IFNAR2	ENST00000342136.9	TSL:1 MANE Select	c.841-220_841-218delGCTinsAGC		intron	N/A	ENSP00000343957.5	P48551-1

Frequencies

GnomAD3 genomes Cov.: 30

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

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.77

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: chr21-34634878;