11-2136949-T-C

Position:

• chr11-2136949-T-C

Variant summary

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

The NM_000612.6(IGF2):​c.-7+1280A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.682 in 152,024 control chromosomes in the GnomAD database, including 36,089 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 0.68 (36089 hom., cov: 34)
• Consequence: IGF2 NM_000612.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.544

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGF2	NM_000612.6	c.-7+1280A>G		intron_variant		ENST00000416167.7
INS-IGF2	NR_003512.4	n.709-1420A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGF2	ENST00000416167.7	c.-7+1280A>G		intron_variant		1	NM_000612.6	P4
	ENST00000643349.2	c.*47-1420A>G		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.681 AC: 103524 AN: 151906 Hom.: 36047 Cov.: 34

Gnomad AFR AF: 0.836

Gnomad AMI AF: 0.561

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.704

Gnomad SAS AF: 0.678

Gnomad FIN AF: 0.589

Gnomad MID AF: 0.672

Gnomad NFE AF: 0.624

Gnomad OTH AF: 0.686

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

GnomAD4 genome AF: 0.682 AC: 103614 AN: 152024 Hom.: 36089 Cov.: 34 AF XY: 0.676 AC XY: 50247 AN XY: 74276

Gnomad4 AFR AF: 0.836

Gnomad4 AMR AF: 0.591

Gnomad4 ASJ AF: 0.639

Gnomad4 EAS AF: 0.703

Gnomad4 SAS AF: 0.677

Gnomad4 FIN AF: 0.589

Gnomad4 NFE AF: 0.624

Gnomad4 OTH AF: 0.686

Alfa AF: 0.628 Hom.: 29872

Bravo AF: 0.691

Asia WGS AF: 0.693 AC: 2409 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.1
DANN	Benign	0.61

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: rs3213216; hg19: chr11-2158179;