11-2134646-C-T

Position:

• chr11-2134646-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.157+721G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0768 in 152,198 control chromosomes in the GnomAD database, including 512 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 0.077 (512 hom., cov: 33)
• Consequence: IGF2 NM_000612.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.663

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGF2	NM_000612.6	c.157+721G>A		intron_variant		ENST00000416167.7
INS-IGF2	NR_003512.4	n.871+721G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGF2	ENST00000416167.7	c.157+721G>A		intron_variant		1	NM_000612.6	P4
	ENST00000643349.2	c.*209+721G>A		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.0768 AC: 11683 AN: 152080 Hom.: 512 Cov.: 33

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.0486

Gnomad ASJ AF: 0.0337

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.0558

Gnomad FIN AF: 0.0725

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0732

Gnomad OTH AF: 0.0511

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

GnomAD4 genome AF: 0.0768 AC: 11691 AN: 152198 Hom.: 512 Cov.: 33 AF XY: 0.0755 AC XY: 5619 AN XY: 74422

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.0485

Gnomad4 ASJ AF: 0.0337

Gnomad4 EAS AF: 0.000581

Gnomad4 SAS AF: 0.0557

Gnomad4 FIN AF: 0.0725

Gnomad4 NFE AF: 0.0732

Gnomad4 OTH AF: 0.0506

Alfa AF: 0.0740 Hom.: 170

Bravo AF: 0.0767

Asia WGS AF: 0.0340 AC: 119 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.9
DANN	Benign	0.38
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3213229; hg19: chr11-2155876; COSMIC: COSV56099410; COSMIC: COSV56099410;