6-160093509-T-C

Position:

• chr6-160093509-T-C

Variant summary

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

The ENST00000356956.6(IGF2R):​c.6656-2930T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 575,932 control chromosomes in the GnomAD database, including 57,111 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 (16323 hom., cov: 32)
  • Exomes 𝑓: 0.43 (40788 hom.)
• Consequence: IGF2R ENST00000356956.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.943

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]

CHP1P2 (HGNC:54896): (CHP1 pseudogene 2) This locus on chromosome 6q25.3 represents a single-exon transcribed pseudogene of the multi-exon calcium binding protein P22 gene which resides on chromosome 15q13.3. This pseudogene is situated within an intron region of the insulin-like growth factor 2 receptor gene (IGF2R). [provided by RefSeq, Jan 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGF2R	NM_000876.4	c.6656-2930T>C		intron_variant		ENST00000356956.6	NP_000867.3
CHP1P2	NR_003288.2	n.428T>C		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGF2R	ENST00000356956.6	c.6656-2930T>C		intron_variant		1	NM_000876.4	ENSP00000349437	P1
CHP1P2	ENST00000366273.3	n.87T>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68727 AN: 151840 Hom.: 16281 Cov.: 32

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.674

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.380

Gnomad OTH AF: 0.447

GnomAD4 exome AF: 0.429 AC: 181807 AN: 423974 Hom.: 40788 Cov.: 0 AF XY: 0.429 AC XY: 99287 AN XY: 231204

Gnomad4 AFR exome AF: 0.587

Gnomad4 AMR exome AF: 0.495

Gnomad4 ASJ exome AF: 0.369

Gnomad4 EAS exome AF: 0.687

Gnomad4 SAS exome AF: 0.478

Gnomad4 FIN exome AF: 0.367

Gnomad4 NFE exome AF: 0.387

Gnomad4 OTH exome AF: 0.424

GnomAD4 genome AF: 0.453 AC: 68816 AN: 151958 Hom.: 16323 Cov.: 32 AF XY: 0.452 AC XY: 33611 AN XY: 74292

Gnomad4 AFR AF: 0.577

Gnomad4 AMR AF: 0.446

Gnomad4 ASJ AF: 0.379

Gnomad4 EAS AF: 0.674

Gnomad4 SAS AF: 0.468

Gnomad4 FIN AF: 0.359

Gnomad4 NFE AF: 0.380

Gnomad4 OTH AF: 0.453

Alfa AF: 0.404 Hom.: 21448

Bravo AF: 0.468

Asia WGS AF: 0.600 AC: 2086 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	2.8
DANN	Benign	0.62

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: rs1888727; hg19: chr6-160514541; COSMIC: COSV63482176; COSMIC: COSV63482176;