rs894817
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1
The NM_000876.4(IGF2R):c.1590G>A(p.Gly530=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 1,613,798 control chromosomes in the GnomAD database, including 95,465 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.32 ( 8485 hom., cov: 33)
Exomes 𝑓: 0.34 ( 86980 hom. )
Consequence
IGF2R
NM_000876.4 synonymous
NM_000876.4 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.628
Genes affected
IGF2R (HGNC:5467): (insulin like growth factor 2 receptor) This gene encodes a receptor for both insulin-like growth factor 2 and mannose 6-phosphate. The binding sites for each ligand are located on different segments of the protein. This receptor has various functions, including in the intracellular trafficking of lysosomal enzymes, the activation of transforming growth factor beta, and the degradation of insulin-like growth factor 2. Mutation or loss of heterozygosity of this gene has been association with risk of hepatocellular carcinoma. The orthologous mouse gene is imprinted and shows exclusive expression from the maternal allele; however, imprinting of the human gene may be polymorphic, as only a minority of individuals showed biased expression from the maternal allele (PMID:8267611). [provided by RefSeq, Nov 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP7
?
Synonymous conserved (PhyloP=0.628 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.727 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IGF2R | NM_000876.4 | c.1590G>A | p.Gly530= | synonymous_variant | 12/48 | ENST00000356956.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IGF2R | ENST00000356956.6 | c.1590G>A | p.Gly530= | synonymous_variant | 12/48 | 1 | NM_000876.4 | P1 | |
IGF2R | ENST00000677704.1 | c.1590G>A | p.Gly530= | synonymous_variant, NMD_transcript_variant | 12/49 | ||||
IGF2R | ENST00000676781.1 | c.1590G>A | p.Gly530= | synonymous_variant, NMD_transcript_variant | 12/49 |
Frequencies
GnomAD3 genomes ? AF: 0.322 AC: 48887AN: 152052Hom.: 8478 Cov.: 33
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GnomAD3 exomes AF: 0.362 AC: 90935AN: 251384Hom.: 18488 AF XY: 0.359 AC XY: 48809AN XY: 135860
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GnomAD4 exome AF: 0.335 AC: 489673AN: 1461628Hom.: 86980 Cov.: 36 AF XY: 0.336 AC XY: 244100AN XY: 727112
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GnomAD4 genome ? AF: 0.321 AC: 48904AN: 152170Hom.: 8485 Cov.: 33 AF XY: 0.323 AC XY: 24050AN XY: 74394
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Not reported inComputational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at