11-2134646-C-T

Variant names:

• chr11-2134646-C-T
• rs3213229
• NM_000612.6:c.157+721G>A

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+721G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0768 in 152,198 control chromosomes in the GnomAD database, including 512 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 0.077 (512 hom., cov: 33)
• Consequence: IGF2 NM_000612.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.663
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF2	NM_000612.6	c.157+721G>A		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+721G>A		intron_variant	Intron 2 of 3	1	NM_000612.6	ENSP00000414497.2
IGF2	ENST00000381392.5	c.157+721G>A		intron_variant	Intron 2 of 3	1		ENSP00000370799.1
IGF2	ENST00000381406.8	c.157+721G>A		intron_variant	Intron 2 of 3	2		ENSP00000370813.4
ENSG00000284779	ENST00000643349.2	c.*209+721G>A		intron_variant	Intron 3 of 4			ENSP00000495715.1

Frequencies

GnomAD3 genomes AF: 0.0768 AC: 11683 AN: 152080 Hom.: 512 Cov.: 33

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.0486

Gnomad ASJ AF: 0.0337

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.0558

Gnomad FIN AF: 0.0725

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0732

Gnomad OTH AF: 0.0511

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

GnomAD4 genome AF: 0.0768 AC: 11691 AN: 152198 Hom.: 512 Cov.: 33 AF XY: 0.0755 AC XY: 5619 AN XY: 74422

African (AFR) AF: 0.110 AC: 4569 AN: 41522

American (AMR) AF: 0.0485 AC: 743 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0337 AC: 117 AN: 3472

East Asian (EAS) AF: 0.000581 AC: 3 AN: 5164

South Asian (SAS) AF: 0.0557 AC: 269 AN: 4832

European-Finnish (FIN) AF: 0.0725 AC: 769 AN: 10612

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0732 AC: 4978 AN: 67970

Other (OTH) AF: 0.0506 AC: 107 AN: 2114

Alfa AF: 0.0734 Hom.: 259

Bravo AF: 0.0767

Asia WGS AF: 0.0340 AC: 119 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	4.9
DANN	Benign	0.38
PhyloP100		-0.66
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: rs3213229; hg19: chr11-2155876; COSMIC: COSV56099410; COSMIC: COSV56099410;