IL12RB2 p.Gln426Gln

Variant names:

• chr1-67367841-C-C
• NM_001374259.2:c.

Your query was ambiguous. Multiple possible variants found:

• chr1-67367842--
• chr1-67367844-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001374259.2(IL12RB2):​c. variant causes a 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: IL12RB2 NM_001374259.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.165
• Publications: 0 publications found

Genes affected

IL12RB2 (HGNC:5972): (interleukin 12 receptor subunit beta 2) The protein encoded by this gene is a type I transmembrane protein identified as a subunit of the interleukin 12 receptor complex. The coexpression of this and IL12RB1 proteins was shown to lead to the formation of high-affinity IL12 binding sites and reconstitution of IL12 dependent signaling. The expression of this gene is up-regulated by interferon gamma in Th1 cells, and plays a role in Th1 cell differentiation. The up-regulation of this gene is found to be associated with a number of infectious diseases, such as Crohn's disease and leprosy, which is thought to contribute to the inflammatory response and host defense. Several transcript variants encoding different isoforms and non-protein coding transcripts have been found for this gene. [provided by RefSeq, Apr 2012]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001374259.2. 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
	IL12RB2	NM_001374259.2	MANE Select	c.		intron	N/A	NP_001361188.1	Q99665-1
	IL12RB2	NM_001559.3		c.		intron	N/A	NP_001550.1	Q99665-1
	IL12RB2	NM_001258215.1		c.		intron	N/A	NP_001245144.1	Q99665-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL12RB2	ENST00000674203.2	MANE Select	c.		intron	N/A	ENSP00000501329.1	Q99665-1
	IL12RB2	ENST00000262345.5	TSL:1	c.		intron	N/A	ENSP00000262345.1	Q99665-1
	IL12RB2	ENST00000544434.5	TSL:1	c.		intron	N/A	ENSP00000442443.1	Q99665-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.17

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: chr1-67833524;