dbSNP rs3802971: IGF2:c.*2165C>T (chr11-2130822-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0770

Publications

17 publications found

Variant links:

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]

IGF2 links:

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]

INS-IGF2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF2	NM_000612.6 link	c.*2165C>T		3_prime_UTR_variant	Exon 4 of 4	ENST00000416167.7	NP_000603.1	P01344-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
IGF2	ENST00000416167.7 link	c.*2165C>T	3_prime_UTR_variant	Exon 4 of 4	1	NM_000612.6	ENSP00000414497.2	P01344-1
IGF2	ENST00000381406.8 link	c.*2165C>T	3_prime_UTR_variant	Exon 4 of 4	2		ENSP00000370813.4	P01344-2
IGF2	ENST00000381395.5 link	c.*2165C>T	3_prime_UTR_variant	Exon 4 of 4	2		ENSP00000370802.1	P01344-1

Frequencies

GnomAD3 genomes

AF:

0.204

AC:

13739

AN:

67212

Hom.:

714

Cov.:

show subpopulations

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.:

AF XY:

0.468

AC XY:

1825

AN XY:

3902

show subpopulations

African (AFR)

AF:

0.405

AC:

102

AN:

252

American (AMR)

AF:

0.390

AC:

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:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AF:

0.525

AC:

AN:

European-Non Finnish (NFE)

AF:

0.400

AC:

1477

AN:

3690

Other (OTH)

AF:

0.436

AC:

231

AN:

530

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

148

295

443

590

738

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.204

AC:

13733

AN:

67252

Hom.:

713

Cov.:

AF XY:

0.211

AC XY:

6785

AN XY:

32170

show subpopulations

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:

AN:

116

European-Non Finnish (NFE)

AF:

0.166

AC:

5571

AN:

33564

Other (OTH)

AF:

0.196

AC:

174

AN:

890

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

579

1158

1737

2316

2895

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

158

316

474

632

790

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

6.1

(source)

DANN

Benign

0.93

PhyloP100

-0.077

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over