11-2131311-C-G

Position:

• chr11-2131311-C-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP5 BP4 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. Variant has been reported in Lovd as Likely pathogenic (no stars).

• 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

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:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• PP5: Variant 11-2131311-C-G is Pathogenic according to our data. Variant chr11-2131311-C-G is described in Lovd as [Likely_pathogenic].
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95). . Strength limited to SUPPORTING due to the PP5.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGF2	NM_000612.6	c.*1676G>C		3_prime_UTR_variant	4/4	ENST00000416167.7
INS-IGF2	NR_003512.4	n.2933G>C		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGF2	ENST00000416167.7	c.*1676G>C		3_prime_UTR_variant	4/4	1	NM_000612.6	P4
IGF2	ENST00000381395.5	c.*1676G>C		3_prime_UTR_variant	4/4	2		P4
IGF2	ENST00000381406.8	c.*1676G>C		3_prime_UTR_variant	4/4	2		A1

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

Gnomad4 AFR exome AF: 0.774

Gnomad4 AMR exome AF: 0.797

Gnomad4 ASJ exome AF: 0.706

Gnomad4 EAS exome AF: 0.555

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.853

Gnomad4 NFE exome AF: 0.704

Gnomad4 OTH exome AF: 0.703

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

Gnomad4 AFR AF: 0.781

Gnomad4 AMR AF: 0.770

Gnomad4 ASJ AF: 0.701

Gnomad4 EAS AF: 0.486

Gnomad4 SAS AF: 0.513

Gnomad4 FIN AF: 0.736

Gnomad4 NFE AF: 0.712

Gnomad4 OTH AF: 0.718

Alfa AF: 0.646 Hom.: 1875

Bravo AF: 0.734

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.2
DANN	Benign	0.48

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

LitVar

Other links and lift over

dbSNP: rs3168310; hg19: chr11-2152541;