rs10945645

chr6-159984392-G-Achr6-159984392-G-T

Variant summary

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

The NM_000876.4(IGF2R):c.150-6792G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,096 control chromosomes in the GnomAD database, including 2,891 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 0.18 (2891 hom., cov: 32)
• Consequence: IGF2R NM_000876.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.531

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGF2R	NM_000876.4	c.150-6792G>A		intron_variant		ENST00000356956.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGF2R	ENST00000356956.6	c.150-6792G>A		intron_variant		1	NM_000876.4	P1
IGF2R	ENST00000676781.1	c.150-6792G>A		intron_variant, NMD_transcript_variant
IGF2R	ENST00000677704.1	c.150-6792G>A		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.178 AC: 26995 AN: 151978 Hom.: 2879 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.0699

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.178 AC: 27034 AN: 152096 Hom.: 2891 Cov.: 32 AF XY: 0.187 AC XY: 13912 AN XY: 74352

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.0699

Gnomad4 EAS AF: 0.456

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.268

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.167

Alfa AF: 0.114 Hom.: 378

Bravo AF: 0.182

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	3.8
Dann	Benign	0.50

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: rs10945645; hg19: chr6-160405424;