rs3832385

chr6-160105872-TCAAA-Tchr6-160105872-TCAAA-TCAAACAAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000876.4(IGF2R):c.*792_*795del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 151,684 control chromosomes in the GnomAD database, including 5,581 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.27 (5566 hom., cov: 20)
  • Exomes 𝑓: 0.24 (15 hom.)
• Consequence: IGF2R NM_000876.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGF2R	NM_000876.4	c.*792_*795del		3_prime_UTR_variant	48/48	ENST00000356956.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGF2R	ENST00000356956.6	c.*792_*795del		3_prime_UTR_variant	48/48	1	NM_000876.4	P1

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40629 AN: 151084 Hom.: 5560 Cov.: 20

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.275

GnomAD4 exome AF: 0.239 AC: 115 AN: 482 Hom.: 15 AF XY: 0.243 AC XY: 73 AN XY: 300

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.235

Gnomad4 NFE exome AF: 0.239

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.269 AC: 40668 AN: 151202 Hom.: 5566 Cov.: 20 AF XY: 0.269 AC XY: 19831 AN XY: 73806

Gnomad4 AFR AF: 0.243

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.429

Gnomad4 SAS AF: 0.268

Gnomad4 FIN AF: 0.244

Gnomad4 NFE AF: 0.268

Gnomad4 OTH AF: 0.279

Alfa AF: 0.268 Hom.: 674

Bravo AF: 0.280

Asia WGS AF: 0.362 AC: 1261 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs3832385; hg19: chr6-160526904;