6-160086446-A-G

Variant summary

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

The NM_000876.4(IGF2R):c.6205+1315A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 151,988 control chromosomes in the GnomAD database, including 15,218 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 0.44 (15218 hom., cov: 32)
• Consequence: IGF2R NM_000876.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGF2R	NM_000876.4	c.6205+1315A>G		intron_variant		ENST00000356956.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGF2R	ENST00000356956.6	c.6205+1315A>G		intron_variant		1	NM_000876.4	P1

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66718 AN: 151870 Hom.: 15177 Cov.: 32

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.394

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.670

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.380

Gnomad OTH AF: 0.438

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

GnomAD4 genome AF: 0.440 AC: 66803 AN: 151988 Hom.: 15218 Cov.: 32 AF XY: 0.440 AC XY: 32721 AN XY: 74306

Gnomad4 AFR AF: 0.530

Gnomad4 AMR AF: 0.442

Gnomad4 ASJ AF: 0.379

Gnomad4 EAS AF: 0.670

Gnomad4 SAS AF: 0.467

Gnomad4 FIN AF: 0.364

Gnomad4 NFE AF: 0.380

Gnomad4 OTH AF: 0.444

Alfa AF: 0.416 Hom.: 2115

Bravo AF: 0.453

Asia WGS AF: 0.596 AC: 2071 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	4.2
Dann	Benign	0.42

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: rs3798178; hg19: chr6-160507478;