chr6-160081695-T-C

Variant names:

• chr6-160081695-T-C
• rs2343275
• NM_000876.4:c.5833+1420T>C

Variant summary

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

The NM_000876.4(IGF2R):​c.5833+1420T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 152,080 control chromosomes in the GnomAD database, including 16,292 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 0.45 (16292 hom., cov: 33)
• Consequence: IGF2R NM_000876.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 3 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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF2R	NM_000876.4	c.5833+1420T>C		intron_variant	Intron 39 of 47	ENST00000356956.6	NP_000867.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGF2R	ENST00000356956.6	c.5833+1420T>C		intron_variant	Intron 39 of 47	1	NM_000876.4	ENSP00000349437.1
IGF2R	ENST00000650503.1	n.2443+1420T>C		intron_variant	Intron 16 of 23
IGF2R	ENST00000676781.1	n.*3941+1420T>C		intron_variant	Intron 40 of 48			ENSP00000504419.1
IGF2R	ENST00000677704.1	n.*1704+1420T>C		intron_variant	Intron 40 of 48			ENSP00000503314.1

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68691 AN: 151962 Hom.: 16250 Cov.: 33

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.380

Gnomad OTH AF: 0.446

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.452 AC: 68780 AN: 152080 Hom.: 16292 Cov.: 33 AF XY: 0.452 AC XY: 33585 AN XY: 74336

African (AFR) AF: 0.576 AC: 23899 AN: 41486

American (AMR) AF: 0.445 AC: 6802 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 1313 AN: 3464

East Asian (EAS) AF: 0.668 AC: 3458 AN: 5174

South Asian (SAS) AF: 0.468 AC: 2260 AN: 4826

European-Finnish (FIN) AF: 0.359 AC: 3789 AN: 10562

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.380 AC: 25797 AN: 67972

Other (OTH) AF: 0.452 AC: 953 AN: 2110

Alfa AF: 0.417 Hom.: 1692

Bravo AF: 0.467

Asia WGS AF: 0.598 AC: 2079 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.89
DANN	Benign	0.24
PhyloP100		-1.3
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: rs2343275; hg19: chr6-160502727; COSMIC: COSV63627647; COSMIC: COSV63627647;