11-2150371-T-C

Variant summary

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

The NR_003512.4(INS-IGF2):n.247-1026A>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 152,120 control chromosomes in the GnomAD database, including 3,158 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 0.19 (3158 hom., cov: 32)
• Consequence: INS-IGF2 NR_003512.4 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0200

Genes affected

INS-IGF2 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INS-IGF2	NR_003512.4	n.247-1026A>G		intron_variant, non_coding_transcript_variant
INS-IGF2	NM_001042376.3	c.188-1026A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGF2	ENST00000481781.3	c.-468-1026A>G		intron_variant		5		P4
IGF2	ENST00000476874.1	n.71-1026A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29166 AN: 152002 Hom.: 3161 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.212

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.192 AC: 29167 AN: 152120 Hom.: 3158 Cov.: 32 AF XY: 0.197 AC XY: 14638 AN XY: 74358

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.166

Gnomad4 ASJ AF: 0.247

Gnomad4 EAS AF: 0.526

Gnomad4 SAS AF: 0.369

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.212

Alfa AF: 0.197 Hom.: 5085

Bravo AF: 0.189

Asia WGS AF: 0.407 AC: 1417 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	3.0
Dann	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4320932; hg19: chr11-2171601;