rs2282140

Variant names:

• chr6-160073489-C-T
• rs2282140
• NM_000876.4:c.4947+20C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000876.4(IGF2R):​c.4947+20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,612,580 control chromosomes in the GnomAD database, including 16,447 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 0.14 (1590 hom., cov: 33)
  • Exomes 𝑓: 0.14 (14857 hom.)
• Consequence: IGF2R NM_000876.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.16
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF2R	NM_000876.4	c.4947+20C>T		intron_variant	Intron 34 of 47	ENST00000356956.6	NP_000867.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGF2R	ENST00000356956.6	c.4947+20C>T		intron_variant	Intron 34 of 47	1	NM_000876.4	ENSP00000349437.1

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21098 AN: 152182 Hom.: 1589 Cov.: 33

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.161

GnomAD2 exomes AF: 0.143 AC: 35525 AN: 248054 AF XY: 0.147

Gnomad AFR exome AF: 0.137

Gnomad AMR exome AF: 0.0993

Gnomad ASJ exome AF: 0.210

Gnomad EAS exome AF: 0.243

Gnomad FIN exome AF: 0.114

Gnomad NFE exome AF: 0.132

Gnomad OTH exome AF: 0.153

GnomAD4 exome AF: 0.139 AC: 202333 AN: 1460280 Hom.: 14857 Cov.: 36 AF XY: 0.140 AC XY: 101986 AN XY: 726320

African (AFR) AF: 0.130 AC: 4356 AN: 33464

American (AMR) AF: 0.104 AC: 4643 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 5513 AN: 26086

East Asian (EAS) AF: 0.241 AC: 9559 AN: 39682

South Asian (SAS) AF: 0.170 AC: 14636 AN: 86164

European-Finnish (FIN) AF: 0.114 AC: 6027 AN: 52902

Middle Eastern (MID) AF: 0.272 AC: 1565 AN: 5762

European-Non Finnish (NFE) AF: 0.132 AC: 146712 AN: 1111172

Other (OTH) AF: 0.154 AC: 9322 AN: 60350

GnomAD4 genome AF: 0.139 AC: 21116 AN: 152300 Hom.: 1590 Cov.: 33 AF XY: 0.138 AC XY: 10284 AN XY: 74476

African (AFR) AF: 0.133 AC: 5526 AN: 41560

American (AMR) AF: 0.128 AC: 1953 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 737 AN: 3472

East Asian (EAS) AF: 0.241 AC: 1248 AN: 5188

South Asian (SAS) AF: 0.178 AC: 858 AN: 4826

European-Finnish (FIN) AF: 0.119 AC: 1259 AN: 10606

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8919 AN: 68024

Other (OTH) AF: 0.165 AC: 348 AN: 2112

Alfa AF: 0.138 Hom.: 2287

Bravo AF: 0.139

Asia WGS AF: 0.210 AC: 728 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0050
DANN	Benign	0.64
PhyloP100		-3.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2282140; hg19: chr6-160494521; COSMIC: COSV107447517;