11-2130822-G-C

Variant names:

• chr11-2130822-G-C
• rs3802971
• NM_000612.6:c.*2165C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000612.6(IGF2):​c.*2165C>G 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 0.000089 (0 hom., cov: 14)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF2	NM_000612.6	c.*2165C>G		3_prime_UTR_variant	Exon 4 of 4	ENST00000416167.7	NP_000603.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGF2	ENST00000416167.7	c.*2165C>G		3_prime_UTR_variant	Exon 4 of 4	1	NM_000612.6	ENSP00000414497.2
IGF2	ENST00000381406.8	c.*2165C>G		3_prime_UTR_variant	Exon 4 of 4	2		ENSP00000370813.4
IGF2	ENST00000381395.5	c.*2165C>G		3_prime_UTR_variant	Exon 4 of 4	2		ENSP00000370802.1

Frequencies

GnomAD3 genomes AF: 0.0000893 AC: 6 AN: 67214 Hom.: 0 Cov.: 14

Gnomad AFR AF: 0.000230

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000549

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000298

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 8248 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 3914

African (AFR) AF: 0.00 AC: 0 AN: 252

American (AMR) AF: 0.00 AC: 0 AN: 164

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 484

East Asian (EAS) AF: 0.00 AC: 0 AN: 3024

South Asian (SAS) AF: 0.00 AC: 0 AN: 44

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 42

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 3704

Other (OTH) AF: 0.00 AC: 0 AN: 532

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000892 AC: 6 AN: 67252 Hom.: 0 Cov.: 14 AF XY: 0.0000622 AC XY: 2 AN XY: 32174

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000229 AC: 4 AN: 17430

American (AMR) AF: 0.00 AC: 0 AN: 5174

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1872

East Asian (EAS) AF: 0.00 AC: 0 AN: 2638

South Asian (SAS) AF: 0.000550 AC: 1 AN: 1818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 116

European-Non Finnish (NFE) AF: 0.0000298 AC: 1 AN: 33556

Other (OTH) AF: 0.00 AC: 0 AN: 886

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000412196), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 1209

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	2.9
DANN	Benign	0.91
PhyloP100		-0.077

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: rs3802971; hg19: chr11-2152052;