rs2297362

chr6-160078533-T-Cchr6-160078533-T-G

Variant summary

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

The NM_000876.4(IGF2R):c.5478+171T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,192 control chromosomes in the GnomAD database, including 3,174 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 0.16 (3174 hom., cov: 33)
• Consequence: IGF2R NM_000876.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.426

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGF2R	NM_000876.4	c.5478+171T>C		intron_variant		ENST00000356956.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGF2R	ENST00000356956.6	c.5478+171T>C		intron_variant		1	NM_000876.4	P1
IGF2R	ENST00000676781.1	c.*3586+171T>C		intron_variant, NMD_transcript_variant
IGF2R	ENST00000677704.1	c.*1349+171T>C		intron_variant, NMD_transcript_variant
IGF2R	ENST00000650503.1	n.2088+171T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24674 AN: 152074 Hom.: 3162 Cov.: 33

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.00577

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.0764

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0660

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.162 AC: 24727 AN: 152192 Hom.: 3174 Cov.: 33 AF XY: 0.165 AC XY: 12275 AN XY: 74406

Gnomad4 AFR AF: 0.307

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.00577

Gnomad4 EAS AF: 0.424

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.0764

Gnomad4 NFE AF: 0.0659

Gnomad4 OTH AF: 0.148

Alfa AF: 0.103 Hom.: 366

Bravo AF: 0.180

Asia WGS AF: 0.311 AC: 1084 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	6.2
Dann	Benign	0.61

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: rs2297362; hg19: chr6-160499565; COSMIC: COSV63628842; COSMIC: COSV63628842;