11-2136949-T-C

Variant names:

• chr11-2136949-T-C
• rs3213216
• NM_000612.6:c.-7+1280A>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.-7+1280A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.682 in 152,024 control chromosomes in the GnomAD database, including 36,089 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 0.68 (36089 hom., cov: 34)
• Consequence: IGF2 NM_000612.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.544
• Publications: 16 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.829 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.-7+1280A>G		intron	N/A	NP_000603.1	P01344-1
	IGF2	NM_001127598.3		c.163-1420A>G		intron	N/A	NP_001121070.1	P01344-3
	IGF2	NM_001007139.6		c.-6-1420A>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.-7+1280A>G		intron	N/A	ENSP00000414497.2	P01344-1
	IGF2	ENST00000434045.6	TSL:1	c.163-1420A>G		intron	N/A	ENSP00000391826.2	P01344-3
	IGF2	ENST00000381392.5	TSL:1	c.-7+239A>G		intron	N/A	ENSP00000370799.1	P01344-2

Frequencies

GnomAD3 genomes AF: 0.681 AC: 103524 AN: 151906 Hom.: 36047 Cov.: 34

Gnomad AFR AF: 0.836

Gnomad AMI AF: 0.561

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.704

Gnomad SAS AF: 0.678

Gnomad FIN AF: 0.589

Gnomad MID AF: 0.672

Gnomad NFE AF: 0.624

Gnomad OTH AF: 0.686

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

GnomAD4 genome AF: 0.682 AC: 103614 AN: 152024 Hom.: 36089 Cov.: 34 AF XY: 0.676 AC XY: 50247 AN XY: 74276

African (AFR) AF: 0.836 AC: 34709 AN: 41516

American (AMR) AF: 0.591 AC: 9038 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.639 AC: 2217 AN: 3472

East Asian (EAS) AF: 0.703 AC: 3617 AN: 5142

South Asian (SAS) AF: 0.677 AC: 3265 AN: 4820

European-Finnish (FIN) AF: 0.589 AC: 6203 AN: 10530

Middle Eastern (MID) AF: 0.675 AC: 197 AN: 292

European-Non Finnish (NFE) AF: 0.624 AC: 42404 AN: 67938

Other (OTH) AF: 0.686 AC: 1452 AN: 2116

Alfa AF: 0.636 Hom.: 45977

Bravo AF: 0.691

Asia WGS AF: 0.693 AC: 2409 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.1
DANN	Benign	0.61
PhyloP100		-0.54
PromoterAI		-0.011	Neutral
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: rs3213216; hg19: chr11-2158179;