rs734351

Variant names:

• chr11-2134983-G-A
• rs734351
• NM_000612.6:c.157+384C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-2134983-G-A
• chr11-2134983-G-C
• chr11-2134983-G-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.157+384C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.645 in 152,170 control chromosomes in the GnomAD database, including 32,463 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 0.64 (32463 hom., cov: 34)
• Consequence: IGF2 NM_000612.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35
• Publications: 28 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF2	NM_000612.6	c.157+384C>T		intron_variant	Intron 2 of 3	ENST00000416167.7	NP_000603.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGF2	ENST00000416167.7	c.157+384C>T		intron_variant	Intron 2 of 3	1	NM_000612.6	ENSP00000414497.2
IGF2	ENST00000381392.5	c.157+384C>T		intron_variant	Intron 2 of 3	1		ENSP00000370799.1
IGF2	ENST00000381406.8	c.157+384C>T		intron_variant	Intron 2 of 3	2		ENSP00000370813.4
ENSG00000284779	ENST00000643349.2	c.*209+384C>T		intron_variant	Intron 3 of 4			ENSP00000495715.1

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97973 AN: 152052 Hom.: 32416 Cov.: 34

Gnomad AFR AF: 0.759

Gnomad AMI AF: 0.730

Gnomad AMR AF: 0.696

Gnomad ASJ AF: 0.560

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.602

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.618

Gnomad OTH AF: 0.636

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

GnomAD4 genome AF: 0.645 AC: 98081 AN: 152170 Hom.: 32463 Cov.: 34 AF XY: 0.637 AC XY: 47415 AN XY: 74396

African (AFR) AF: 0.759 AC: 31523 AN: 41526

American (AMR) AF: 0.697 AC: 10659 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.560 AC: 1943 AN: 3472

East Asian (EAS) AF: 0.280 AC: 1445 AN: 5164

South Asian (SAS) AF: 0.405 AC: 1952 AN: 4824

European-Finnish (FIN) AF: 0.602 AC: 6377 AN: 10588

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.618 AC: 42030 AN: 67978

Other (OTH) AF: 0.637 AC: 1347 AN: 2114

Alfa AF: 0.625 Hom.: 105018

Bravo AF: 0.660

Asia WGS AF: 0.386 AC: 1343 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.8
DANN	Benign	0.75
PhyloP100		1.3
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: rs734351; hg19: chr11-2156213; COSMIC: COSV56099418; COSMIC: COSV56099418;