NM_000612.6:c.*29C>T

Variant names:

• chr11-2132958-G-A
• rs2230949
• NM_000612.6:c.*29C>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.*29C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0732 in 1,409,384 control chromosomes in the GnomAD database, including 4,159 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 0.062 (346 hom., cov: 32)
  • Exomes 𝑓: 0.075 (3813 hom.)
• Consequence: IGF2 NM_000612.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.570
• Publications: 17 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 (NFE) allele frequency at 95% confidence interval = 0.0748 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.*29C>T		3_prime_UTR	Exon 4 of 4	NP_000603.1	P01344-1
	IGF2	NM_001127598.3		c.*29C>T		3_prime_UTR	Exon 5 of 5	NP_001121070.1	P01344-3
	IGF2	NM_001007139.6		c.*29C>T		3_prime_UTR	Exon 5 of 5	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.*29C>T		3_prime_UTR	Exon 4 of 4	ENSP00000414497.2	P01344-1
	IGF2	ENST00000434045.6	TSL:1	c.*29C>T		3_prime_UTR	Exon 5 of 5	ENSP00000391826.2	P01344-3
	IGF2	ENST00000381392.5	TSL:1	c.*29C>T		3_prime_UTR	Exon 4 of 4	ENSP00000370799.1	P01344-2

Frequencies

GnomAD3 genomes AF: 0.0621 AC: 9439 AN: 152052 Hom.: 345 Cov.: 32

Gnomad AFR AF: 0.0434

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0584

Gnomad ASJ AF: 0.0925

Gnomad EAS AF: 0.000966

Gnomad SAS AF: 0.0404

Gnomad FIN AF: 0.0795

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0765

Gnomad OTH AF: 0.0780

GnomAD2 exomes AF: 0.0626 AC: 9683 AN: 154750 AF XY: 0.0642

Gnomad AFR exome AF: 0.0426

Gnomad AMR exome AF: 0.0435

Gnomad ASJ exome AF: 0.109

Gnomad EAS exome AF: 0.000464

Gnomad FIN exome AF: 0.0781

Gnomad NFE exome AF: 0.0789

Gnomad OTH exome AF: 0.0637

GnomAD4 exome AF: 0.0746 AC: 93737 AN: 1257214 Hom.: 3813 Cov.: 19 AF XY: 0.0741 AC XY: 45828 AN XY: 618456

African (AFR) AF: 0.0416 AC: 1134 AN: 27228

American (AMR) AF: 0.0465 AC: 1197 AN: 25740

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 1964 AN: 19128

East Asian (EAS) AF: 0.000339 AC: 12 AN: 35386

South Asian (SAS) AF: 0.0460 AC: 3062 AN: 66562

European-Finnish (FIN) AF: 0.0791 AC: 3833 AN: 48448

Middle Eastern (MID) AF: 0.0645 AC: 320 AN: 4958

European-Non Finnish (NFE) AF: 0.0804 AC: 78571 AN: 977562

Other (OTH) AF: 0.0698 AC: 3644 AN: 52202

GnomAD4 genome AF: 0.0620 AC: 9436 AN: 152170 Hom.: 346 Cov.: 32 AF XY: 0.0617 AC XY: 4589 AN XY: 74414

African (AFR) AF: 0.0433 AC: 1799 AN: 41540

American (AMR) AF: 0.0584 AC: 892 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0925 AC: 321 AN: 3470

East Asian (EAS) AF: 0.000968 AC: 5 AN: 5166

South Asian (SAS) AF: 0.0402 AC: 194 AN: 4824

European-Finnish (FIN) AF: 0.0795 AC: 843 AN: 10602

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0766 AC: 5204 AN: 67964

Other (OTH) AF: 0.0767 AC: 162 AN: 2112

Alfa AF: 0.0753 Hom.: 881

Bravo AF: 0.0616

Asia WGS AF: 0.0180 AC: 61 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.6
DANN	Benign	0.74
PhyloP100		0.57
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)		0.020		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: rs2230949; hg19: chr11-2154188; COSMIC: COSV56098188; COSMIC: COSV56098188;