11-2135700-G-A

Variant names:

• chr11-2135700-G-A
• rs3213223
• NM_000612.6:c.-6-171C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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]

ENSG00000284779 (HGNC:):

INS-IGF2 (HGNC:33527): (INS-IGF2 readthrough) This locus includes two alternatively spliced read-through transcript variants which align to the INS gene in the 5' region and to the IGF2 gene in the 3' region. One transcript is predicted to encode a protein which shares the N-terminus with the INS protein but has a distinct and longer C-terminus, whereas the other transcript is a candidate for nonsense-mediated decay (NMD). The transcripts are imprinted and are paternally expressed in the limb and eye. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000612.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF2	NM_000612.6	MANE Select	c.-6-171C>T		intron	N/A	NP_000603.1
	IGF2	NM_001127598.3		c.163-171C>T		intron	N/A	NP_001121070.1
	IGF2	NM_001007139.6		c.-6-171C>T		intron	N/A	NP_001007140.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF2	ENST00000416167.7	TSL:1 MANE Select	c.-6-171C>T		intron	N/A	ENSP00000414497.2
	IGF2	ENST00000434045.6	TSL:1	c.163-171C>T		intron	N/A	ENSP00000391826.2
	IGF2	ENST00000381392.5	TSL:1	c.-6-171C>T		intron	N/A	ENSP00000370799.1

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

African (AFR) AF: 0.0421 AC: 1750 AN: 41560

American (AMR) AF: 0.152 AC: 2331 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 678 AN: 3472

East Asian (EAS) AF: 0.0847 AC: 439 AN: 5180

South Asian (SAS) AF: 0.0967 AC: 467 AN: 4830

European-Finnish (FIN) AF: 0.173 AC: 1836 AN: 10608

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.219 AC: 14913 AN: 67988

Other (OTH) AF: 0.156 AC: 331 AN: 2116

Alfa AF: 0.189 Hom.: 5262

Bravo AF: 0.146

Asia WGS AF: 0.115 AC: 399 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.4
DANN	Benign	0.63
PhyloP100		-0.81
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3213223; hg19: chr11-2156930;