11-2132404-T-C

Variant names:

• chr11-2132404-T-C
• rs680
• NM_000612.6:c.*583A>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.*583A>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 0.751 in 189,340 control chromosomes in the GnomAD database, including 54,770 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 0.77 (45986 hom., cov: 29)
  • Exomes 𝑓: 0.68 (8784 hom.)
• Consequence: IGF2 NM_000612.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.651
• Publications: 104 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.917 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.*583A>G		3_prime_UTR	Exon 4 of 4	NP_000603.1	P01344-1
	IGF2	NM_001127598.3		c.*583A>G		3_prime_UTR	Exon 5 of 5	NP_001121070.1	P01344-3
	IGF2	NM_001007139.6		c.*583A>G		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.*583A>G		3_prime_UTR	Exon 4 of 4	ENSP00000414497.2	P01344-1
	IGF2	ENST00000381406.8	TSL:2	c.*583A>G		3_prime_UTR	Exon 4 of 4	ENSP00000370813.4	P01344-2
	ENSG00000284779	ENST00000643349.2		c.*1178A>G		3_prime_UTR	Exon 5 of 5	ENSP00000495715.1	A0A2R8Y747

Frequencies

GnomAD3 genomes AF: 0.770 AC: 116783 AN: 151702 Hom.: 45911 Cov.: 29

Gnomad AFR AF: 0.925

Gnomad AMI AF: 0.789

Gnomad AMR AF: 0.788

Gnomad ASJ AF: 0.711

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.746

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.719

Gnomad OTH AF: 0.754

GnomAD4 exome AF: 0.676 AC: 25347 AN: 37520 Hom.: 8784 Cov.: 0 AF XY: 0.675 AC XY: 11726 AN XY: 17364

African (AFR) AF: 0.919 AC: 1334 AN: 1452

American (AMR) AF: 0.796 AC: 707 AN: 888

Ashkenazi Jewish (ASJ) AF: 0.691 AC: 1616 AN: 2340

East Asian (EAS) AF: 0.565 AC: 3922 AN: 6936

South Asian (SAS) AF: 0.435 AC: 135 AN: 310

European-Finnish (FIN) AF: 0.750 AC: 33 AN: 44

Middle Eastern (MID) AF: 0.561 AC: 137 AN: 244

European-Non Finnish (NFE) AF: 0.689 AC: 15359 AN: 22276

Other (OTH) AF: 0.694 AC: 2104 AN: 3030

GnomAD4 genome AF: 0.770 AC: 116920 AN: 151820 Hom.: 45986 Cov.: 29 AF XY: 0.764 AC XY: 56696 AN XY: 74172

African (AFR) AF: 0.925 AC: 38310 AN: 41410

American (AMR) AF: 0.789 AC: 12023 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.711 AC: 2467 AN: 3470

East Asian (EAS) AF: 0.494 AC: 2540 AN: 5140

South Asian (SAS) AF: 0.505 AC: 2424 AN: 4802

European-Finnish (FIN) AF: 0.746 AC: 7850 AN: 10520

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

European-Non Finnish (NFE) AF: 0.719 AC: 48820 AN: 67920

Other (OTH) AF: 0.754 AC: 1592 AN: 2112

Alfa AF: 0.746 Hom.: 14773

Bravo AF: 0.784

Asia WGS AF: 0.551 AC: 1918 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.2
DANN	Benign	0.69
PhyloP100		-0.65
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: rs680; hg19: chr11-2153634;