11-2135814-C-G

Variant names:

• chr11-2135814-C-G
• rs3213221
• NM_000612.6:c.-6-285G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000612.6(IGF2):​c.-6-285G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 152,116 control chromosomes in the GnomAD database, including 24,310 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 0.55 (24310 hom., cov: 34)
• Consequence: IGF2 NM_000612.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.336
• Publications: 26 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.671 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF2	NM_000612.6	MANE Select	c.-6-285G>C		intron	N/A	NP_000603.1	P01344-1
	IGF2	NM_001127598.3		c.163-285G>C		intron	N/A	NP_001121070.1	P01344-3
	IGF2	NM_001007139.6		c.-6-285G>C		intron	N/A	NP_001007140.2	P01344-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF2	ENST00000416167.7	TSL:1 MANE Select	c.-6-285G>C		intron	N/A	ENSP00000414497.2	P01344-1
	IGF2	ENST00000434045.6	TSL:1	c.163-285G>C		intron	N/A	ENSP00000391826.2	P01344-3
	IGF2	ENST00000381392.5	TSL:1	c.-6-285G>C		intron	N/A	ENSP00000370799.1	P01344-2

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84371 AN: 151998 Hom.: 24290 Cov.: 34

Gnomad AFR AF: 0.440

Gnomad AMI AF: 0.731

Gnomad AMR AF: 0.681

Gnomad ASJ AF: 0.566

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.618

Gnomad OTH AF: 0.571

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

GnomAD4 genome AF: 0.555 AC: 84416 AN: 152116 Hom.: 24310 Cov.: 34 AF XY: 0.551 AC XY: 40993 AN XY: 74360

African (AFR) AF: 0.440 AC: 18229 AN: 41470

American (AMR) AF: 0.682 AC: 10433 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.566 AC: 1964 AN: 3468

East Asian (EAS) AF: 0.281 AC: 1457 AN: 5176

South Asian (SAS) AF: 0.405 AC: 1956 AN: 4830

European-Finnish (FIN) AF: 0.603 AC: 6387 AN: 10600

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.618 AC: 41985 AN: 67958

Other (OTH) AF: 0.572 AC: 1210 AN: 2116

Alfa AF: 0.471 Hom.: 1386

Bravo AF: 0.561

Asia WGS AF: 0.362 AC: 1259 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.0
DANN	Benign	0.35
PhyloP100		-0.34
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: rs3213221; hg19: chr11-2157044;