NM_000612.6:c.*2165C>T

Variant names:

• chr11-2130822-G-A
• rs3802971
• NM_000612.6:c.*2165C>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.*2165C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. 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 0.20 (713 hom., cov: 14)
  • Exomes 𝑓: 0.47 (323 hom.)
• Consequence: IGF2 NM_000612.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0770
• Publications: 17 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.332 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.*2165C>T		3_prime_UTR	Exon 4 of 4	NP_000603.1	P01344-1
	IGF2	NM_001127598.3		c.*2165C>T		3_prime_UTR	Exon 5 of 5	NP_001121070.1	P01344-3
	IGF2	NM_001007139.6		c.*2165C>T		3_prime_UTR	Exon 5 of 5	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.*2165C>T		3_prime_UTR	Exon 4 of 4	ENSP00000414497.2	P01344-1
	IGF2	ENST00000381406.8	TSL:2	c.*2165C>T		3_prime_UTR	Exon 4 of 4	ENSP00000370813.4	P01344-2
	IGF2	ENST00000381395.5	TSL:2	c.*2165C>T		3_prime_UTR	Exon 4 of 4	ENSP00000370802.1	P01344-1

Frequencies

GnomAD3 genomes AF: 0.204 AC: 13739 AN: 67212 Hom.: 714 Cov.: 14

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.197

GnomAD4 exome AF: 0.466 AC: 3827 AN: 8220 Hom.: 323 Cov.: 0 AF XY: 0.468 AC XY: 1825 AN XY: 3902

African (AFR) AF: 0.405 AC: 102 AN: 252

American (AMR) AF: 0.390 AC: 64 AN: 164

Ashkenazi Jewish (ASJ) AF: 0.475 AC: 230 AN: 484

East Asian (EAS) AF: 0.558 AC: 1681 AN: 3014

South Asian (SAS) AF: 0.455 AC: 20 AN: 44

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AF: 0.525 AC: 21 AN: 40

European-Non Finnish (NFE) AF: 0.400 AC: 1477 AN: 3690

Other (OTH) AF: 0.436 AC: 231 AN: 530

GnomAD4 genome AF: 0.204 AC: 13733 AN: 67252 Hom.: 713 Cov.: 14 AF XY: 0.211 AC XY: 6785 AN XY: 32170

African (AFR) AF: 0.225 AC: 3922 AN: 17424

American (AMR) AF: 0.220 AC: 1143 AN: 5186

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 431 AN: 1874

East Asian (EAS) AF: 0.351 AC: 922 AN: 2628

South Asian (SAS) AF: 0.183 AC: 332 AN: 1812

European-Finnish (FIN) AF: 0.346 AC: 1160 AN: 3350

Middle Eastern (MID) AF: 0.259 AC: 30 AN: 116

European-Non Finnish (NFE) AF: 0.166 AC: 5571 AN: 33564

Other (OTH) AF: 0.196 AC: 174 AN: 890

Alfa AF: 0.0878 Hom.: 1209

Bravo AF: 0.0951

Asia WGS AF: 0.145 AC: 503 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.077
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3802971; hg19: chr11-2152052;