rs121912426
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP2PP3_Strong
The NM_000875.5(IGF1R):c.413G>A(p.Arg138Gln) variant causes a missense change involving the alteration of a conserved nucleotide. 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 protective (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
IGF1R
NM_000875.5 missense
NM_000875.5 missense
Scores
11
7
1
Clinical Significance
Conservation
PhyloP100: 9.86
Genes affected
IGF1R (HGNC:5465): (insulin like growth factor 1 receptor) This receptor binds insulin-like growth factor with a high affinity. It has tyrosine kinase activity. The insulin-like growth factor I receptor plays a critical role in transformation events. Cleavage of the precursor generates alpha and beta subunits. It is highly overexpressed in most malignant tissues where it functions as an anti-apoptotic agent by enhancing cell survival. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, May 2014]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in the IGF1R gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 12 curated pathogenic missense variants (we use a threshold of 10). The gene has 19 curated benign missense variants. Trascript score misZ: 4.6449 (above the threshold of 3.09). GenCC associations: The gene is linked to growth delay due to insulin-like growth factor I resistance.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.968
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| IGF1R | ENST00000650285.1 | c.413G>A | p.Arg138Gln | missense_variant | Exon 2 of 21 | NM_000875.5 | ENSP00000497069.1 | |||
| IGF1R | ENST00000559925.5 | n.413G>A | non_coding_transcript_exon_variant | Exon 2 of 10 | 1 | |||||
| IGF1R | ENST00000649865.1 | c.413G>A | p.Arg138Gln | missense_variant | Exon 2 of 21 | ENSP00000496919.1 | ||||
| IGF1R | ENST00000558355.1 | c.50G>A | p.Arg17Gln | missense_variant | Exon 1 of 2 | 2 | ENSP00000453630.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 33
GnomAD4 exome
Cov.:
33
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Significance: protective
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Growth delay due to insulin-like growth factor I resistance Benign:1
Dec 04, 2003
OMIM
Significance: protective
Review Status: no assertion criteria provided
Collection Method: literature only
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Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Pathogenic
D;.;D;.;D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;.;D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M;.;M;.;.
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
.;.;D;D;D
REVEL
Pathogenic
Sift
Uncertain
.;.;D;D;D
Sift4G
Uncertain
.;.;D;D;D
Polyphen
D;D;D;D;.
Vest4
0.96, 0.90
MutPred
Loss of MoRF binding (P = 0.027);Loss of MoRF binding (P = 0.027);Loss of MoRF binding (P = 0.027);Loss of MoRF binding (P = 0.027);.;
MVP
0.94
MPC
1.7
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at