rs2585

chr11-2129214-T-Cchr11-2129214-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000612.6(IGF2):c.*3773A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.742 in 198,006 control chromosomes in the GnomAD database, including 55,627 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 0.76 (44652 hom., cov: 32)
  • Exomes 𝑓: 0.68 (10975 hom.)
• Consequence: IGF2 NM_000612.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24

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 -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 = 0.893 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGF2	NM_000612.6	c.*3773A>G		3_prime_UTR_variant	4/4	ENST00000416167.7
INS-IGF2	NR_003512.4	n.5030A>G		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGF2	ENST00000416167.7	c.*3773A>G		3_prime_UTR_variant	4/4	1	NM_000612.6	P4
	ENST00000430034.1	n.280A>G		non_coding_transcript_exon_variant	2/2	3
IGF2	ENST00000381395.5	c.*3773A>G		3_prime_UTR_variant	4/4	2		P4
IGF2	ENST00000381406.8	c.*3773A>G		3_prime_UTR_variant	4/4	2		A1

Frequencies

GnomAD3 genomes AF: 0.759 AC: 115340 AN: 151904 Hom.: 44589 Cov.: 32

Gnomad AFR AF: 0.900

Gnomad AMI AF: 0.795

Gnomad AMR AF: 0.783

Gnomad ASJ AF: 0.695

Gnomad EAS AF: 0.488

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.739

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.713

Gnomad OTH AF: 0.741

GnomAD4 exome AF: 0.684 AC: 31474 AN: 45984 Hom.: 10975 Cov.: 0 AF XY: 0.683 AC XY: 14561 AN XY: 21328

Gnomad4 AFR exome AF: 0.881

Gnomad4 AMR exome AF: 0.814

Gnomad4 ASJ exome AF: 0.701

Gnomad4 EAS exome AF: 0.550

Gnomad4 SAS exome AF: 0.485

Gnomad4 FIN exome AF: 0.806

Gnomad4 NFE exome AF: 0.703

Gnomad4 OTH exome AF: 0.698

GnomAD4 genome AF: 0.760 AC: 115467 AN: 152022 Hom.: 44652 Cov.: 32 AF XY: 0.753 AC XY: 55983 AN XY: 74302

Gnomad4 AFR AF: 0.900

Gnomad4 AMR AF: 0.784

Gnomad4 ASJ AF: 0.695

Gnomad4 EAS AF: 0.488

Gnomad4 SAS AF: 0.514

Gnomad4 FIN AF: 0.739

Gnomad4 NFE AF: 0.713

Gnomad4 OTH AF: 0.741

Alfa AF: 0.719 Hom.: 39759

Bravo AF: 0.773

Asia WGS AF: 0.551 AC: 1918 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	0.76
Dann	Benign	0.59

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: rs2585; hg19: chr11-2150444;