11-2132404-T-C

Position:

• chr11-2132404-T-C

Variant summary

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

The ENST00000416167.7(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. Variant has been reported in Lovd as Likely pathogenic (no stars).

• Frequency:
  • Genomes: 𝑓 0.77 (45986 hom., cov: 29)
  • Exomes 𝑓: 0.68 (8784 hom.)
• Consequence: IGF2 ENST00000416167.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.651

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.917 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGF2	NM_000612.6	c.*583A>G		3_prime_UTR_variant	4/4	ENST00000416167.7	NP_000603.1
INS-IGF2	NR_003512.4	n.1840A>G		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGF2	ENST00000416167.7	c.*583A>G		3_prime_UTR_variant	4/4	1	NM_000612.6	ENSP00000414497	P4
	ENST00000643349.2	c.*1178A>G		3_prime_UTR_variant	5/5			ENSP00000495715	P1

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

Gnomad4 AFR exome AF: 0.919

Gnomad4 AMR exome AF: 0.796

Gnomad4 ASJ exome AF: 0.691

Gnomad4 EAS exome AF: 0.565

Gnomad4 SAS exome AF: 0.435

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.689

Gnomad4 OTH exome AF: 0.694

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

Gnomad4 AFR AF: 0.925

Gnomad4 AMR AF: 0.789

Gnomad4 ASJ AF: 0.711

Gnomad4 EAS AF: 0.494

Gnomad4 SAS AF: 0.505

Gnomad4 FIN AF: 0.746

Gnomad4 NFE AF: 0.719

Gnomad4 OTH AF: 0.754

Alfa AF: 0.747 Hom.: 8880

Bravo AF: 0.784

Asia WGS AF: 0.551 AC: 1918 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.2
DANN	Benign	0.69

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: rs680; hg19: chr11-2153634;