rs8191821

chr6-160050720-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000876.4(IGF2R):c.2694+68C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0579 in 1,396,136 control chromosomes in the GnomAD database, including 4,803 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 0.058 (601 hom., cov: 32)
  • Exomes 𝑓: 0.058 (4202 hom.)
• Consequence: IGF2R NM_000876.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGF2R	NM_000876.4	c.2694+68C>T		intron_variant		ENST00000356956.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGF2R	ENST00000356956.6	c.2694+68C>T		intron_variant		1	NM_000876.4	P1
IGF2R	ENST00000676781.1	c.*802+68C>T		intron_variant, NMD_transcript_variant
IGF2R	ENST00000677704.1	c.2694+68C>T		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0575 AC: 8749 AN: 152126 Hom.: 596 Cov.: 32

Gnomad AFR AF: 0.0127

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.0499

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0466

Gnomad OTH AF: 0.0512

GnomAD4 exome AF: 0.0580 AC: 72117 AN: 1243892 Hom.: 4202 AF XY: 0.0586 AC XY: 35749 AN XY: 610466

Gnomad4 AFR exome AF: 0.0101

Gnomad4 AMR exome AF: 0.224

Gnomad4 ASJ exome AF: 0.00781

Gnomad4 EAS exome AF: 0.314

Gnomad4 SAS exome AF: 0.105

Gnomad4 FIN exome AF: 0.0572

Gnomad4 NFE exome AF: 0.0427

Gnomad4 OTH exome AF: 0.0577

GnomAD4 genome AF: 0.0575 AC: 8757 AN: 152244 Hom.: 601 Cov.: 32 AF XY: 0.0605 AC XY: 4508 AN XY: 74454

Gnomad4 AFR AF: 0.0127

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.00490

Gnomad4 EAS AF: 0.324

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.0499

Gnomad4 NFE AF: 0.0466

Gnomad4 OTH AF: 0.0563

Alfa AF: 0.0510 Hom.: 460

Bravo AF: 0.0659

Asia WGS AF: 0.216 AC: 752 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	3.9
Dann	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs8191821; hg19: chr6-160471752; COSMIC: COSV63631854;