chr15-98649583-T-A
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000875.5(IGF1R):c.2T>A(p.Met1?) variant causes a start lost change involving the alteration of a non-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 Likely pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
IGF1R
NM_000875.5 start_lost
NM_000875.5 start_lost
Scores
3
1
7
Clinical Significance
Conservation
PhyloP100: 3.19
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 Pathogenic. Variant got 12 ACMG points.
PVS1
?
Start lost variant, no new inframe start found.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 15-98649583-T-A is Pathogenic according to our data. Variant chr15-98649583-T-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2664702.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IGF1R | NM_000875.5 | c.2T>A | p.Met1? | start_lost | 1/21 | ENST00000650285.1 | |
IRAIN | NR_126453.2 | n.1205A>T | non_coding_transcript_exon_variant | 1/1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IGF1R | ENST00000650285.1 | c.2T>A | p.Met1? | start_lost | 1/21 | NM_000875.5 | P4 | ||
IGF1R | ENST00000559925.5 | n.2T>A | non_coding_transcript_exon_variant | 1/10 | 1 | ||||
IGF1R | ENST00000649865.1 | c.2T>A | p.Met1? | start_lost | 1/21 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 25
GnomAD4 exome
Cov.:
25
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Growth delay due to insulin-like growth factor I resistance Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Genetics and Molecular Pathology, SA Pathology | Jun 09, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Benign
DEOGEN2
Benign
T;.;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D
Polyphen
P;P;P;P
Vest4
0.86, 0.78
MutPred
Loss of stability (P = 0.0012);Loss of stability (P = 0.0012);Loss of stability (P = 0.0012);Loss of stability (P = 0.0012);
MVP
0.90
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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
Publications
No publications associated with this variant yet.