chr11-2148678-T-C

Position:

• chr11-2148678-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000643349.2(ENSG00000284779):​c.254+448A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 177,588 control chromosomes in the GnomAD database, including 11,460 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 0.36 (9824 hom., cov: 31)
  • Exomes 𝑓: 0.33 (1636 hom.)
• Consequence: ENST00000643349.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.899

Genes affected

(HGNC:):

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-AS (HGNC:14062): (IGF2 antisense RNA) This gene is expressed in antisense to the insulin-like growth factor 2 (IGF2) gene and is imprinted and paternally expressed. It is thought to be non-coding because the putative protein is not conserved and translation is predicted to trigger nonsense mediated decay (NMD). Transcripts from this gene are produced in tumors and may function to suppress cell growth. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INS-IGF2	NR_003512.4	n.466+448A>G		intron_variant, non_coding_transcript_variant
IGF2-AS	NR_028043.2			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000643349.2	c.254+448A>G		intron_variant				ENSP00000495715	P1
IGF2	ENST00000481781.3	c.-249+448A>G		intron_variant		5		ENSP00000511998	P4
IGF2	ENST00000695541.1	c.-249+448A>G		intron_variant				ENSP00000511997	P4
IGF2-AS	ENST00000381361.4			downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54102 AN: 151636 Hom.: 9821 Cov.: 31

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.328

GnomAD4 exome AF: 0.331 AC: 8547 AN: 25834 Hom.: 1636 Cov.: 0 AF XY: 0.324 AC XY: 4246 AN XY: 13086

Gnomad4 AFR exome AF: 0.342

Gnomad4 AMR exome AF: 0.285

Gnomad4 ASJ exome AF: 0.319

Gnomad4 EAS exome AF: 0.252

Gnomad4 SAS exome AF: 0.266

Gnomad4 FIN exome AF: 0.308

Gnomad4 NFE exome AF: 0.352

Gnomad4 OTH exome AF: 0.347

GnomAD4 genome AF: 0.357 AC: 54126 AN: 151754 Hom.: 9824 Cov.: 31 AF XY: 0.351 AC XY: 25997 AN XY: 74120

Gnomad4 AFR AF: 0.386

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.332

Gnomad4 EAS AF: 0.279

Gnomad4 SAS AF: 0.266

Gnomad4 FIN AF: 0.339

Gnomad4 NFE AF: 0.372

Gnomad4 OTH AF: 0.329

Alfa AF: 0.160 Hom.: 263

Bravo AF: 0.354

Asia WGS AF: 0.313 AC: 1091 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.3
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs3741204; hg19: chr11-2169908;