11-2131311-C-G

Variant names:

• chr11-2131311-C-G
• rs3168310
• NM_000612.6:c.*1676G>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.*1676G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.711 in 233,194 control chromosomes in the GnomAD database, including 59,598 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 0.72 (40323 hom., cov: 34)
  • Exomes 𝑓: 0.69 (19275 hom.)
• Consequence: IGF2 NM_000612.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0910
• Publications: 11 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]

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]

ENSG00000284779 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.774 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.*1676G>C		3_prime_UTR	Exon 4 of 4	NP_000603.1
	INS-IGF2	NR_003512.4		n.2933G>C		non_coding_transcript_exon	Exon 7 of 7
	IGF2	NM_001127598.3		c.*1676G>C		3_prime_UTR	Exon 5 of 5	NP_001121070.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF2	ENST00000416167.7	TSL:1 MANE Select	c.*1676G>C		3_prime_UTR	Exon 4 of 4	ENSP00000414497.2
	IGF2	ENST00000381406.8	TSL:2	c.*1676G>C		3_prime_UTR	Exon 4 of 4	ENSP00000370813.4
	IGF2	ENST00000381395.5	TSL:2	c.*1676G>C		3_prime_UTR	Exon 4 of 4	ENSP00000370802.1

Frequencies

GnomAD3 genomes AF: 0.724 AC: 110179 AN: 152094 Hom.: 40275 Cov.: 34

Gnomad AFR AF: 0.781

Gnomad AMI AF: 0.786

Gnomad AMR AF: 0.769

Gnomad ASJ AF: 0.701

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.736

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.712

Gnomad OTH AF: 0.717

GnomAD4 exome AF: 0.687 AC: 55601 AN: 80982 Hom.: 19275 Cov.: 0 AF XY: 0.686 AC XY: 25555 AN XY: 37236

African (AFR) AF: 0.774 AC: 3012 AN: 3892

American (AMR) AF: 0.797 AC: 1987 AN: 2494

Ashkenazi Jewish (ASJ) AF: 0.706 AC: 3608 AN: 5114

East Asian (EAS) AF: 0.555 AC: 6328 AN: 11406

South Asian (SAS) AF: 0.500 AC: 353 AN: 706

European-Finnish (FIN) AF: 0.853 AC: 58 AN: 68

Middle Eastern (MID) AF: 0.553 AC: 272 AN: 492

European-Non Finnish (NFE) AF: 0.704 AC: 35219 AN: 50034

Other (OTH) AF: 0.703 AC: 4764 AN: 6776

GnomAD4 genome AF: 0.725 AC: 110289 AN: 152212 Hom.: 40323 Cov.: 34 AF XY: 0.721 AC XY: 53645 AN XY: 74398

African (AFR) AF: 0.781 AC: 32456 AN: 41542

American (AMR) AF: 0.770 AC: 11775 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.701 AC: 2431 AN: 3468

East Asian (EAS) AF: 0.486 AC: 2505 AN: 5158

South Asian (SAS) AF: 0.513 AC: 2475 AN: 4826

European-Finnish (FIN) AF: 0.736 AC: 7795 AN: 10592

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.712 AC: 48455 AN: 68014

Other (OTH) AF: 0.718 AC: 1516 AN: 2112

Alfa AF: 0.646 Hom.: 1875

Bravo AF: 0.734

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.2
DANN	Benign	0.48
PhyloP100		-0.091
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: rs3168310; hg19: chr11-2152541;