rs6909681

Positions:

• chr6-160048067-T-A

Variant summary

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

The NM_000876.4(IGF2R):​c.2345+160T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 152,146 control chromosomes in the GnomAD database, including 21,870 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 0.53 (21870 hom., cov: 33)
• Consequence: IGF2R NM_000876.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.125

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGF2R	NM_000876.4	c.2345+160T>A		intron_variant		ENST00000356956.6	NP_000867.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGF2R	ENST00000356956.6	c.2345+160T>A		intron_variant		1	NM_000876.4	ENSP00000349437	P1
IGF2R	ENST00000676781.1	c.*453+160T>A		intron_variant, NMD_transcript_variant				ENSP00000504419
IGF2R	ENST00000677704.1	c.2345+160T>A		intron_variant, NMD_transcript_variant				ENSP00000503314

Frequencies

GnomAD3 genomes AF: 0.533 AC: 80956 AN: 152028 Hom.: 21826 Cov.: 33

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.589

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.530

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

GnomAD4 genome AF: 0.533 AC: 81049 AN: 152146 Hom.: 21870 Cov.: 33 AF XY: 0.537 AC XY: 39917 AN XY: 74370

Gnomad4 AFR AF: 0.604

Gnomad4 AMR AF: 0.513

Gnomad4 ASJ AF: 0.441

Gnomad4 EAS AF: 0.671

Gnomad4 SAS AF: 0.517

Gnomad4 FIN AF: 0.589

Gnomad4 NFE AF: 0.481

Gnomad4 OTH AF: 0.535

Alfa AF: 0.518 Hom.: 2550

Bravo AF: 0.532

Asia WGS AF: 0.624 AC: 2170 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.4
DANN	Benign	0.59

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: rs6909681; hg19: chr6-160469099; COSMIC: COSV63627593;