rs3213225

Variant names:

• chr11-2135306-G-A
• rs3213225
• NM_000612.6:c.157+61C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-2135306-G-A
• chr11-2135306-G-T

Variant summary

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

The NM_000612.6(IGF2):​c.157+61C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.59 in 1,430,540 control chromosomes in the GnomAD database, including 254,737 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 0.55 (23558 hom., cov: 34)
  • Exomes 𝑓: 0.60 (231179 hom.)
• Consequence: IGF2 NM_000612.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.185
• Publications: 15 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF2	NM_000612.6	c.157+61C>T		intron_variant	Intron 2 of 3	ENST00000416167.7	NP_000603.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGF2	ENST00000416167.7	c.157+61C>T		intron_variant	Intron 2 of 3	1	NM_000612.6	ENSP00000414497.2
IGF2	ENST00000381392.5	c.157+61C>T		intron_variant	Intron 2 of 3	1		ENSP00000370799.1
IGF2	ENST00000381406.8	c.157+61C>T		intron_variant	Intron 2 of 3	2		ENSP00000370813.4
ENSG00000284779	ENST00000643349.2	c.*209+61C>T		intron_variant	Intron 3 of 4			ENSP00000495715.1

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82890 AN: 151980 Hom.: 23533 Cov.: 34

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.662

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.601

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.616

Gnomad OTH AF: 0.559

GnomAD4 exome AF: 0.595 AC: 761180 AN: 1278442 Hom.: 231179 AF XY: 0.590 AC XY: 368083 AN XY: 624232

African (AFR) AF: 0.400 AC: 11337 AN: 28320

American (AMR) AF: 0.718 AC: 18060 AN: 25152

Ashkenazi Jewish (ASJ) AF: 0.560 AC: 11318 AN: 20220

East Asian (EAS) AF: 0.285 AC: 9664 AN: 33906

South Asian (SAS) AF: 0.400 AC: 26367 AN: 65874

European-Finnish (FIN) AF: 0.611 AC: 28271 AN: 46302

Middle Eastern (MID) AF: 0.447 AC: 2255 AN: 5048

European-Non Finnish (NFE) AF: 0.624 AC: 624135 AN: 1000716

Other (OTH) AF: 0.563 AC: 29773 AN: 52904

GnomAD4 genome AF: 0.545 AC: 82944 AN: 152098 Hom.: 23558 Cov.: 34 AF XY: 0.542 AC XY: 40293 AN XY: 74348

African (AFR) AF: 0.418 AC: 17324 AN: 41480

American (AMR) AF: 0.663 AC: 10147 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.546 AC: 1894 AN: 3472

East Asian (EAS) AF: 0.282 AC: 1458 AN: 5176

South Asian (SAS) AF: 0.397 AC: 1915 AN: 4828

European-Finnish (FIN) AF: 0.601 AC: 6360 AN: 10580

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.616 AC: 41872 AN: 67944

Other (OTH) AF: 0.561 AC: 1183 AN: 2110

Alfa AF: 0.535 Hom.: 6304

Bravo AF: 0.548

Asia WGS AF: 0.359 AC: 1246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.6
DANN	Benign	0.69
PhyloP100		-0.18
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs3213225; hg19: chr11-2156536; COSMIC: COSV56098470; COSMIC: COSV56098470;