dbSNP rs1821322134: IL11RA:p.Gln28ArgfsTer17 (chr9-34655294-GC-G) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PVS1_StrongPM2

The NM_001142784.3(IL11RA):c.82delC(p.Gln28ArgfsTer17) variant causes a frameshift 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: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

IL11RA
NM_001142784.3 frameshift

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.311

Publications

0 publications found

Variant links:

Genes affected

IL11RA (HGNC:5967): (interleukin 11 receptor subunit alpha) Interleukin 11 is a stromal cell-derived cytokine that belongs to a family of pleiotropic and redundant cytokines that use the gp130 transducing subunit in their high affinity receptors. This gene encodes the IL-11 receptor, which is a member of the hematopoietic cytokine receptor family. This particular receptor is very similar to ciliary neurotrophic factor, since both contain an extracellular region with a 2-domain structure composed of an immunoglobulin-like domain and a cytokine receptor-like domain. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2012]

IL11RA Gene-Disease associations (from GenCC):

craniosynostosis and dental anomalies
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet, ClinGen

IL11RA links:

ENSG00000258728 (HGNC:):

ENSG00000258728 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 18 pathogenic variants in the truncated region.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142784.3. 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
	IL11RA	NM_001142784.3	MANE Select	c.82delC	p.Gln28ArgfsTer17	frameshift	Exon 2 of 13	NP_001136256.1	Q14626-1
	IL11RA	NR_052010.2		n.169delC		non_coding_transcript_exon	Exon 2 of 13

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL11RA	ENST00000441545.7	TSL:5 MANE Select	c.82delC	p.Gln28ArgfsTer17	frameshift	Exon 2 of 13	ENSP00000394391.3	Q14626-1
IL11RA	ENST00000318041.13	TSL:1	c.82delC	p.Gln28ArgfsTer17	frameshift	Exon 2 of 13	ENSP00000326500.8	Q14626-1
IL11RA	ENST00000602473.5	TSL:1	c.82delC	p.Gln28ArgfsTer17	frameshift	Exon 1 of 10	ENSP00000473647.1	Q14626-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1457704

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724946

African (AFR)

AF:

0.00

AC:

AN:

33422

American (AMR)

AF:

0.00

AC:

AN:

44420

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26004

East Asian (EAS)

AF:

0.00

AC:

AN:

39630

South Asian (SAS)

AF:

0.00

AC:

AN:

85506

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53170

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109564

Other (OTH)

AF:

0.00

AC:

AN:

60226

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over