11-2131409-C-T

Position:

• chr11-2131409-C-T

Variant summary

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

The NM_000612.6(IGF2):​c.*1578G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0374 in 233,074 control chromosomes in the GnomAD database, including 249 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 0.037 (156 hom., cov: 34)
  • Exomes 𝑓: 0.038 (93 hom.)
• Consequence: IGF2 NM_000612.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.452

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGF2	NM_000612.6	c.*1578G>A		3_prime_UTR_variant	4/4	ENST00000416167.7
INS-IGF2	NR_003512.4	n.2835G>A		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGF2	ENST00000416167.7	c.*1578G>A		3_prime_UTR_variant	4/4	1	NM_000612.6	P4
	ENST00000643349.2	c.*2173G>A		3_prime_UTR_variant	5/5			P1

Frequencies

GnomAD3 genomes AF: 0.0369 AC: 5612 AN: 151924 Hom.: 158 Cov.: 34

Gnomad AFR AF: 0.00975

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0176

Gnomad ASJ AF: 0.0225

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00932

Gnomad FIN AF: 0.0725

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0578

Gnomad OTH AF: 0.0297

GnomAD4 exome AF: 0.0384 AC: 3113 AN: 81030 Hom.: 93 Cov.: 0 AF XY: 0.0383 AC XY: 1427 AN XY: 37254

Gnomad4 AFR exome AF: 0.00847

Gnomad4 AMR exome AF: 0.0160

Gnomad4 ASJ exome AF: 0.0228

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0225

Gnomad4 FIN exome AF: 0.118

Gnomad4 NFE exome AF: 0.0527

Gnomad4 OTH exome AF: 0.0385

GnomAD4 genome AF: 0.0369 AC: 5611 AN: 152044 Hom.: 156 Cov.: 34 AF XY: 0.0373 AC XY: 2776 AN XY: 74360

Gnomad4 AFR AF: 0.00972

Gnomad4 AMR AF: 0.0175

Gnomad4 ASJ AF: 0.0225

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00974

Gnomad4 FIN AF: 0.0725

Gnomad4 NFE AF: 0.0578

Gnomad4 OTH AF: 0.0294

Alfa AF: 0.0516 Hom.: 105

Bravo AF: 0.0325

Asia WGS AF: 0.00549 AC: 20 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.4
DANN	Benign	0.78
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.2

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: rs1065687; hg19: chr11-2152639;