chr6-160027264-G-A
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_000876.4(IGF2R):c.726G>A(p.Ala242=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000285 in 1,614,132 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000029 ( 0 hom. )
Consequence
IGF2R
NM_000876.4 synonymous
NM_000876.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -4.67
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 -11 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.69).
BP6
?
Variant 6-160027264-G-A is Benign according to our data. Variant chr6-160027264-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2657099.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-4.67 with no splicing effect.
BS2
?
High AC in GnomAdExome at 9 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IGF2R | NM_000876.4 | c.726G>A | p.Ala242= | synonymous_variant | 6/48 | ENST00000356956.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IGF2R | ENST00000356956.6 | c.726G>A | p.Ala242= | synonymous_variant | 6/48 | 1 | NM_000876.4 | P1 | |
IGF2R | ENST00000677704.1 | c.726G>A | p.Ala242= | synonymous_variant, NMD_transcript_variant | 6/49 | ||||
IGF2R | ENST00000676781.1 | c.726G>A | p.Ala242= | synonymous_variant, NMD_transcript_variant | 6/49 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152242Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251046Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135750
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GnomAD4 exome AF: 0.0000294 AC: 43AN: 1461772Hom.: 0 Cov.: 31 AF XY: 0.0000275 AC XY: 20AN XY: 727182
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2023 | IGF2R: BP4, BP7 - |
Computational 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
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at