rs10840452

Positions:

• chr11-2157278-G-A

Variant summary

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

The NR_003512.4(INS-IGF2):​n.246+3507C>T 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 0.278 in 152,206 control chromosomes in the GnomAD database, including 7,000 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 0.28 (7000 hom., cov: 33)
• Consequence: INS-IGF2 NR_003512.4 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.294

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INS-IGF2	NR_003512.4	n.246+3507C>T		intron_variant, non_coding_transcript_variant
INS-IGF2	NM_001042376.3	c.187+3507C>T		intron_variant			NP_001035835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGF2	ENST00000481781.3	c.-469+989C>T		intron_variant		5		ENSP00000511998	P4
IGF2	ENST00000476874.1	n.70+989C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42232 AN: 152088 Hom.: 6991 Cov.: 33

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.302

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

GnomAD4 genome AF: 0.278 AC: 42264 AN: 152206 Hom.: 7000 Cov.: 33 AF XY: 0.282 AC XY: 20946 AN XY: 74408

Gnomad4 AFR AF: 0.100

Gnomad4 AMR AF: 0.392

Gnomad4 ASJ AF: 0.315

Gnomad4 EAS AF: 0.122

Gnomad4 SAS AF: 0.325

Gnomad4 FIN AF: 0.361

Gnomad4 NFE AF: 0.351

Gnomad4 OTH AF: 0.304

Alfa AF: 0.304 Hom.: 1080

Bravo AF: 0.270

Asia WGS AF: 0.215 AC: 748 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	1.7
DANN	Benign	0.88

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: rs10840452; hg19: chr11-2178508;