rs3213233

Variant names:

• chr11-2133691-G-C
• rs3213233
• NM_000612.6:c.158-26C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000612.6(IGF2):​c.158-26C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00516 in 1,611,764 control chromosomes in the GnomAD database, including 320 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 0.026 (165 hom., cov: 33)
  • Exomes 𝑓: 0.0030 (155 hom.)
• Consequence: IGF2 NM_000612.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.438
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0867 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000612.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF2	NM_000612.6	MANE Select	c.158-26C>G		intron	N/A	NP_000603.1	P01344-1
	IGF2	NM_001127598.3		c.326-26C>G		intron	N/A	NP_001121070.1	P01344-3
	IGF2	NM_001007139.6		c.158-26C>G		intron	N/A	NP_001007140.2	P01344-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF2	ENST00000416167.7	TSL:1 MANE Select	c.158-26C>G		intron	N/A	ENSP00000414497.2	P01344-1
	IGF2	ENST00000434045.6	TSL:1	c.326-26C>G		intron	N/A	ENSP00000391826.2	P01344-3
	IGF2	ENST00000381392.5	TSL:1	c.158-17C>G		intron	N/A	ENSP00000370799.1	P01344-2

Frequencies

GnomAD3 genomes AF: 0.0261 AC: 3971 AN: 152196 Hom.: 163 Cov.: 33

Gnomad AFR AF: 0.0890

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00955

Gnomad ASJ AF: 0.0109

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000764

Gnomad OTH AF: 0.0191

GnomAD2 exomes AF: 0.00716 AC: 1739 AN: 242754 AF XY: 0.00549

Gnomad AFR exome AF: 0.0897

Gnomad AMR exome AF: 0.00554

Gnomad ASJ exome AF: 0.00854

Gnomad EAS exome AF: 0.0000550

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000428

Gnomad OTH exome AF: 0.00452

GnomAD4 exome AF: 0.00296 AC: 4324 AN: 1459450 Hom.: 155 Cov.: 31 AF XY: 0.00262 AC XY: 1901 AN XY: 726008

African (AFR) AF: 0.0910 AC: 3041 AN: 33424

American (AMR) AF: 0.00572 AC: 255 AN: 44604

Ashkenazi Jewish (ASJ) AF: 0.00967 AC: 252 AN: 26068

East Asian (EAS) AF: 0.00 AC: 0 AN: 39648

South Asian (SAS) AF: 0.000197 AC: 17 AN: 86078

European-Finnish (FIN) AF: 0.0000192 AC: 1 AN: 52190

Middle Eastern (MID) AF: 0.00486 AC: 27 AN: 5552

European-Non Finnish (NFE) AF: 0.000278 AC: 309 AN: 1111574

Other (OTH) AF: 0.00700 AC: 422 AN: 60312

GnomAD4 genome AF: 0.0262 AC: 3985 AN: 152314 Hom.: 165 Cov.: 33 AF XY: 0.0258 AC XY: 1918 AN XY: 74484

African (AFR) AF: 0.0891 AC: 3701 AN: 41544

American (AMR) AF: 0.00954 AC: 146 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.0109 AC: 38 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.000764 AC: 52 AN: 68030

Other (OTH) AF: 0.0189 AC: 40 AN: 2116

Alfa AF: 0.0138 Hom.: 13

Bravo AF: 0.0294

Asia WGS AF: 0.00606 AC: 22 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.4
DANN	Benign	0.50
PhyloP100		0.44
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: rs3213233; hg19: chr11-2154921;