rs3213217

Variant names:

• chr11-2136563-A-T
• rs3213217
• NM_000612.6:c.-6-1034T>A

Variant summary

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

The NM_000612.6(IGF2):​c.-6-1034T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 152,324 control chromosomes in the GnomAD database, including 2,237 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 0.15 (2237 hom., cov: 34)
• Consequence: IGF2 NM_000612.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.185

Genes affected

IGF2 (HGNC:5466): (insulin like growth factor 2) This gene encodes a member of the insulin family of polypeptide growth factors, which are involved in development and growth. It is an imprinted gene, expressed only from the paternal allele, and epigenetic changes at this locus are associated with Wilms tumour, Beckwith-Wiedemann syndrome, rhabdomyosarcoma, and Silver-Russell syndrome. A read-through INS-IGF2 gene exists, whose 5' region overlaps the INS gene and the 3' region overlaps this gene. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2010]

ENSG00000284779 (HGNC:):

INS-IGF2 (HGNC:33527): (INS-IGF2 readthrough) This locus includes two alternatively spliced read-through transcript variants which align to the INS gene in the 5' region and to the IGF2 gene in the 3' region. One transcript is predicted to encode a protein which shares the N-terminus with the INS protein but has a distinct and longer C-terminus, whereas the other transcript is a candidate for nonsense-mediated decay (NMD). The transcripts are imprinted and are paternally expressed in the limb and eye. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF2	NM_000612.6	c.-6-1034T>A		intron_variant	Intron 1 of 3	ENST00000416167.7	NP_000603.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGF2	ENST00000416167.7	c.-6-1034T>A		intron_variant	Intron 1 of 3	1	NM_000612.6	ENSP00000414497.2
IGF2	ENST00000381392.5	c.-7+625T>A		intron_variant	Intron 1 of 3	1		ENSP00000370799.1
IGF2	ENST00000381406.8	c.-6-1034T>A		intron_variant	Intron 1 of 3	2		ENSP00000370813.4
ENSG00000284779	ENST00000643349.2	c.*47-1034T>A		intron_variant	Intron 2 of 4			ENSP00000495715.1

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23098 AN: 152206 Hom.: 2236 Cov.: 34

Gnomad AFR AF: 0.0418

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.0883

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.152 AC: 23100 AN: 152324 Hom.: 2237 Cov.: 34 AF XY: 0.146 AC XY: 10888 AN XY: 74496

Gnomad4 AFR AF: 0.0417

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.0876

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.172

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.160

Alfa AF: 0.186 Hom.: 410

Bravo AF: 0.146

Asia WGS AF: 0.119 AC: 413 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	6.2
DANN	Benign	0.91
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3213217; hg19: chr11-2157793; COSMIC: COSV56097785; COSMIC: COSV56097785;