6-160078533-T-C

Variant names:

• chr6-160078533-T-C
• rs2297362
• NM_000876.4:c.5478+171T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
IGF2R	NM_000876.4	c.5478+171T>C		intron_variant	Intron 37 of 47	ENST00000356956.6	NP_000867.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGF2R	ENST00000356956.6	c.5478+171T>C		intron_variant	Intron 37 of 47	1	NM_000876.4	ENSP00000349437.1
IGF2R	ENST00000650503.1	n.2088+171T>C		intron_variant	Intron 14 of 23
IGF2R	ENST00000676781.1	n.*3586+171T>C		intron_variant	Intron 38 of 48			ENSP00000504419.1
IGF2R	ENST00000677704.1	n.*1349+171T>C		intron_variant	Intron 38 of 48			ENSP00000503314.1

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

African (AFR) AF: 0.307 AC: 12737 AN: 41504

American (AMR) AF: 0.208 AC: 3177 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00577 AC: 20 AN: 3468

East Asian (EAS) AF: 0.424 AC: 2186 AN: 5156

South Asian (SAS) AF: 0.191 AC: 922 AN: 4822

European-Finnish (FIN) AF: 0.0764 AC: 811 AN: 10614

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0659 AC: 4484 AN: 68012

Other (OTH) AF: 0.148 AC: 313 AN: 2112

Alfa AF: 0.0948 Hom.: 541

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
PhyloP100		-0.43
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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