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. Variant got -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

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=-0.87).
• 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

Gnomad4 AFR exome AF: 0.400

Gnomad4 AMR exome AF: 0.718

Gnomad4 ASJ exome AF: 0.560

Gnomad4 EAS exome AF: 0.285

Gnomad4 SAS exome AF: 0.400

Gnomad4 FIN exome AF: 0.611

Gnomad4 NFE exome AF: 0.624

Gnomad4 OTH exome AF: 0.563

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

Gnomad4 AFR AF: 0.418

Gnomad4 AMR AF: 0.663

Gnomad4 ASJ AF: 0.546

Gnomad4 EAS AF: 0.282

Gnomad4 SAS AF: 0.397

Gnomad4 FIN AF: 0.601

Gnomad4 NFE AF: 0.616

Gnomad4 OTH AF: 0.561

Alfa AF: 0.583 Hom.: 5132

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3213225; hg19: chr11-2156536; COSMIC: COSV56098470; COSMIC: COSV56098470;