rs3802971

Positions:

• chr11-2130822-G-A
• chr11-2130822-G-C

Variant summary

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

The NM_000612.6(IGF2):​c.*2165C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. 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 0.20 (713 hom., cov: 14)
  • Exomes 𝑓: 0.47 (323 hom.)
• Consequence: IGF2 NM_000612.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0770

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]

INS-IGF2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGF2	NM_000612.6	c.*2165C>T		3_prime_UTR_variant	4/4	ENST00000416167.7
INS-IGF2	NR_003512.4	n.3422C>T		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGF2	ENST00000416167.7	c.*2165C>T		3_prime_UTR_variant	4/4	1	NM_000612.6	P4
IGF2	ENST00000381395.5	c.*2165C>T		3_prime_UTR_variant	4/4	2		P4
IGF2	ENST00000381406.8	c.*2165C>T		3_prime_UTR_variant	4/4	2		A1

Frequencies

GnomAD3 genomes AF: 0.204 AC: 13739 AN: 67212 Hom.: 714 Cov.: 14

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.197

GnomAD4 exome AF: 0.466 AC: 3827 AN: 8220 Hom.: 323 Cov.: 0 AF XY: 0.468 AC XY: 1825 AN XY: 3902

Gnomad4 AFR exome AF: 0.405

Gnomad4 AMR exome AF: 0.390

Gnomad4 ASJ exome AF: 0.475

Gnomad4 EAS exome AF: 0.558

Gnomad4 SAS exome AF: 0.455

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.400

Gnomad4 OTH exome AF: 0.436

GnomAD4 genome AF: 0.204 AC: 13733 AN: 67252 Hom.: 713 Cov.: 14 AF XY: 0.211 AC XY: 6785 AN XY: 32170

Gnomad4 AFR AF: 0.225

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.351

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.166

Gnomad4 OTH AF: 0.196

Alfa AF: 0.0864 Hom.: 859

Bravo AF: 0.0951

Asia WGS AF: 0.145 AC: 503 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	6.1
DANN	Benign	0.93
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs3802971; hg19: chr11-2152052;