6-159984392-G-T

Position:

• chr6-159984392-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000356956.6(IGF2R):​c.150-6792G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00591 in 152,148 control chromosomes in the GnomAD database, including 10 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 0.0059 (10 hom., cov: 32)
• Consequence: IGF2R ENST00000356956.6 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=-0.88).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00591 (899/152148) while in subpopulation AFR AF= 0.021 (872/41494). AF 95% confidence interval is 0.0199. There are 10 homozygotes in gnomad4. There are 414 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 899 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGF2R	NM_000876.4	c.150-6792G>T		intron_variant		ENST00000356956.6	NP_000867.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGF2R	ENST00000356956.6	c.150-6792G>T		intron_variant		1	NM_000876.4	ENSP00000349437.1
IGF2R	ENST00000676781.1	n.150-6792G>T		intron_variant				ENSP00000504419.1
IGF2R	ENST00000677704.1	n.150-6792G>T		intron_variant				ENSP00000503314.1

Frequencies

GnomAD3 genomes AF: 0.00591 AC: 898 AN: 152030 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.0211

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00239

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

GnomAD4 genome AF: 0.00591 AC: 899 AN: 152148 Hom.: 10 Cov.: 32 AF XY: 0.00557 AC XY: 414 AN XY: 74388

Gnomad4 AFR AF: 0.0210

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00237

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.52

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;