chr9-34656846-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001142784.3(IL11RA):​c.269G>A​(p.Gly90Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

IL11RA
NM_001142784.3 missense

Scores

5
11
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.38
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.906

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IL11RANM_001142784.3 linkuse as main transcriptc.269G>A p.Gly90Asp missense_variant 4/13 ENST00000441545.7
IL11RANR_052010.2 linkuse as main transcriptn.356G>A non_coding_transcript_exon_variant 4/13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IL11RAENST00000441545.7 linkuse as main transcriptc.269G>A p.Gly90Asp missense_variant 4/135 NM_001142784.3 P4Q14626-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingInvitaeAug 22, 2022In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with IL11RA-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 90 of the IL11RA protein (p.Gly90Asp). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.48
BayesDel_addAF
Pathogenic
0.44
D
BayesDel_noAF
Pathogenic
0.39
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.54
.;D;D;.;D;.;.;.
Eigen
Uncertain
0.62
Eigen_PC
Uncertain
0.59
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Benign
0.84
T;.;.;T;T;T;T;T
M_CAP
Uncertain
0.26
D
MetaRNN
Pathogenic
0.91
D;D;D;D;D;D;D;D
MetaSVM
Uncertain
0.61
D
MutationAssessor
Uncertain
2.8
.;M;M;.;M;.;.;M
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.61
T
PROVEAN
Benign
-0.83
N;D;D;D;D;D;D;.
REVEL
Uncertain
0.58
Sift
Pathogenic
0.0
D;D;D;D;D;D;D;.
Sift4G
Pathogenic
0.0
D;D;D;T;D;T;D;D
Polyphen
1.0
.;D;D;.;D;.;.;.
Vest4
0.91, 0.90, 0.91, 0.90
MutPred
0.79
.;Gain of phosphorylation at Y92 (P = 0.0848);Gain of phosphorylation at Y92 (P = 0.0848);Gain of phosphorylation at Y92 (P = 0.0848);Gain of phosphorylation at Y92 (P = 0.0848);Gain of phosphorylation at Y92 (P = 0.0848);Gain of phosphorylation at Y92 (P = 0.0848);Gain of phosphorylation at Y92 (P = 0.0848);
MVP
0.76
MPC
0.92
ClinPred
0.98
D
GERP RS
4.4
Varity_R
0.89
gMVP
0.91

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-34656843; API