rs3213223

chr11-2135700-G-Achr11-2135700-G-C

Variant summary

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

The NM_000612.6(IGF2):c.-6-171C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 152,260 control chromosomes in the GnomAD database, including 2,246 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 0.15 (2246 hom., cov: 34)
• Consequence: IGF2 NM_000612.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.805

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGF2	NM_000612.6	c.-6-171C>T		intron_variant		ENST00000416167.7
INS-IGF2	NR_003512.4	n.709-171C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGF2	ENST00000416167.7	c.-6-171C>T		intron_variant		1	NM_000612.6	P4
	ENST00000643349.2	c.*47-171C>T		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23063 AN: 152142 Hom.: 2245 Cov.: 34

Gnomad AFR AF: 0.0422

Gnomad AMI AF: 0.335

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.0855

Gnomad SAS AF: 0.0964

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.152 AC: 23068 AN: 152260 Hom.: 2246 Cov.: 34 AF XY: 0.146 AC XY: 10883 AN XY: 74436

Gnomad4 AFR AF: 0.0421

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.0847

Gnomad4 SAS AF: 0.0967

Gnomad4 FIN AF: 0.173

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.156

Alfa AF: 0.192 Hom.: 3272

Bravo AF: 0.146

Asia WGS AF: 0.115 AC: 399 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	1.4
Dann	Benign	0.63

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: rs3213223; hg19: chr11-2156930;