rs2230949

Positions:

• chr11-2132958-G-A
• chr11-2132958-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 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. Variant has been reported in Lovd as Likely benign (no stars).

• 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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 11-2132958-G-A is Benign according to our data. Variant chr11-2132958-G-A is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGF2	NM_000612.6	c.*29C>T		3_prime_UTR_variant	4/4	ENST00000416167.7	NP_000603.1
INS-IGF2	NR_003512.4	n.1286C>T		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGF2	ENST00000416167.7	c.*29C>T		3_prime_UTR_variant	4/4	1	NM_000612.6	ENSP00000414497	P4
	ENST00000643349.2	c.*624C>T		3_prime_UTR_variant	5/5			ENSP00000495715	P1

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

GnomAD3 exomes AF: 0.0626 AC: 9683 AN: 154750 Hom.: 344 AF XY: 0.0642 AC XY: 5370 AN XY: 83626

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 SAS exome AF: 0.0411

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

Gnomad4 AFR exome AF: 0.0416

Gnomad4 AMR exome AF: 0.0465

Gnomad4 ASJ exome AF: 0.103

Gnomad4 EAS exome AF: 0.000339

Gnomad4 SAS exome AF: 0.0460

Gnomad4 FIN exome AF: 0.0791

Gnomad4 NFE exome AF: 0.0804

Gnomad4 OTH exome AF: 0.0698

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

Gnomad4 AFR AF: 0.0433

Gnomad4 AMR AF: 0.0584

Gnomad4 ASJ AF: 0.0925

Gnomad4 EAS AF: 0.000968

Gnomad4 SAS AF: 0.0402

Gnomad4 FIN AF: 0.0795

Gnomad4 NFE AF: 0.0766

Gnomad4 OTH AF: 0.0767

Alfa AF: 0.0786 Hom.: 605

Bravo AF: 0.0616

Asia WGS AF: 0.0180 AC: 61 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.6
DANN	Benign	0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs2230949; hg19: chr11-2154188; COSMIC: COSV56098188; COSMIC: COSV56098188;