rs2585

Variant names:

• chr11-2129214-T-C
• rs2585
• NM_000612.6:c.*3773A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-2129214-T-C
• chr11-2129214-T-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.*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
• Publications: 24 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]

ENSG00000240801 (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 = 0.893 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF2	NM_000612.6	c.*3773A>G		3_prime_UTR_variant	Exon 4 of 4	ENST00000416167.7	NP_000603.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGF2	ENST00000416167.7	c.*3773A>G		3_prime_UTR_variant	Exon 4 of 4	1	NM_000612.6	ENSP00000414497.2
IGF2	ENST00000381406.8	c.*3773A>G		3_prime_UTR_variant	Exon 4 of 4	2		ENSP00000370813.4
ENSG00000240801	ENST00000430034.1	n.280A>G		non_coding_transcript_exon_variant	Exon 2 of 2	3
IGF2	ENST00000381395.5	c.*3773A>G		3_prime_UTR_variant	Exon 4 of 4	2		ENSP00000370802.1

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

African (AFR) AF: 0.881 AC: 1666 AN: 1892

American (AMR) AF: 0.814 AC: 985 AN: 1210

Ashkenazi Jewish (ASJ) AF: 0.701 AC: 2056 AN: 2934

East Asian (EAS) AF: 0.550 AC: 4275 AN: 7770

South Asian (SAS) AF: 0.485 AC: 192 AN: 396

European-Finnish (FIN) AF: 0.806 AC: 29 AN: 36

Middle Eastern (MID) AF: 0.605 AC: 173 AN: 286

European-Non Finnish (NFE) AF: 0.703 AC: 19467 AN: 27690

Other (OTH) AF: 0.698 AC: 2631 AN: 3770

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

African (AFR) AF: 0.900 AC: 37381 AN: 41512

American (AMR) AF: 0.784 AC: 11980 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.695 AC: 2414 AN: 3472

East Asian (EAS) AF: 0.488 AC: 2515 AN: 5152

South Asian (SAS) AF: 0.514 AC: 2470 AN: 4808

European-Finnish (FIN) AF: 0.739 AC: 7786 AN: 10538

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.713 AC: 48457 AN: 67934

Other (OTH) AF: 0.741 AC: 1567 AN: 2114

Alfa AF: 0.727 Hom.: 60667

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
PhyloP100		-1.2
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: rs2585; hg19: chr11-2150444;