IFNAR2 p.Leu23Leu

Variant names:

• chr21-33243683-C-C
• ENST00000342136.9:c.

Your query was ambiguous. Multiple possible variants found:

• chr21-33243684--
• chr21-33243686-C-T
• chr21-33243686-C-A
• chr21-33243686-C-G
• chr21-33243684-CTC-TTA
• chr21-33243684-CTC-TTG

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PVS1_Moderate PM2

The ENST00000342136.9(IFNAR2):​c. variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IFNAR2 ENST00000342136.9 splice_donor, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.986
• 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 4 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.027131783 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000342136.9. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFNAR2	ENST00000342136.9	TSL:1 MANE Select	c.		splice_donor intron	N/A	ENSP00000343957.5	P48551-1
	IFNAR2-IL10RB	ENST00000433395.7	TSL:5	c.		splice_donor intron	N/A	ENSP00000388223.3	H0Y3Z8
	IFNAR2	ENST00000382264.7	TSL:1	c.		splice_donor intron	N/A	ENSP00000371699.3	P48551-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.99

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: chr21-34615988;