rs17101839

Positions:

• chr12-65851788-C-T

Variant summary

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

The NM_003483.6(HMGA2):​c.249+13219C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0746 in 292,012 control chromosomes in the GnomAD database, including 2,027 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 0.11 (1802 hom., cov: 32)
  • Exomes 𝑓: 0.041 (225 hom.)
• Consequence: HMGA2 NM_003483.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

Genes affected

HMGA2 (HGNC:5009): (high mobility group AT-hook 2) This gene encodes a protein that belongs to the non-histone chromosomal high mobility group (HMG) protein family. HMG proteins function as architectural factors and are essential components of the enhancesome. This protein contains structural DNA-binding domains and may act as a transcriptional regulating factor. Identification of the deletion, amplification, and rearrangement of this gene that are associated with myxoid liposarcoma suggests a role in adipogenesis and mesenchymal differentiation. A gene knock out study of the mouse counterpart demonstrated that this gene is involved in diet-induced obesity. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

HMGA2-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMGA2	NM_003483.6	c.249+13219C>T		intron_variant		ENST00000403681.7	NP_003474.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMGA2	ENST00000403681.7	c.249+13219C>T		intron_variant		1	NM_003483.6	ENSP00000384026.2

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15944 AN: 152112 Hom.: 1791 Cov.: 32

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0607

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0505

Gnomad FIN AF: 0.0212

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0322

Gnomad OTH AF: 0.0890

GnomAD4 exome AF: 0.0415 AC: 5799 AN: 139782 Hom.: 225 AF XY: 0.0429 AC XY: 3386 AN XY: 78872

Gnomad4 AFR exome AF: 0.243

Gnomad4 AMR exome AF: 0.0297

Gnomad4 ASJ exome AF: 0.0943

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0553

Gnomad4 FIN exome AF: 0.0254

Gnomad4 NFE exome AF: 0.0285

Gnomad4 OTH exome AF: 0.0480

GnomAD4 genome AF: 0.105 AC: 15997 AN: 152230 Hom.: 1802 Cov.: 32 AF XY: 0.102 AC XY: 7627 AN XY: 74422

Gnomad4 AFR AF: 0.284

Gnomad4 AMR AF: 0.0606

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.000964

Gnomad4 SAS AF: 0.0497

Gnomad4 FIN AF: 0.0212

Gnomad4 NFE AF: 0.0322

Gnomad4 OTH AF: 0.0885

Alfa AF: 0.0768 Hom.: 175

Bravo AF: 0.116

Asia WGS AF: 0.0400 AC: 141 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	0.73
DANN	Benign	0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs17101839; hg19: chr12-66245568;