rs2272047

Positions:

• chr12-65842955-T-C
• chr12-65842955-T-G

Variant summary

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

The ENST00000393578.7(HMGA2):​c.*341T>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 0.0961 in 964,188 control chromosomes in the GnomAD database, including 13,840 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 0.22 (7873 hom., cov: 32)
  • Exomes 𝑓: 0.073 (5967 hom.)
• Consequence: HMGA2 ENST00000393578.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.290

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMGA2	NM_003483.6	c.249+4386T>C		intron_variant		ENST00000403681.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMGA2	ENST00000403681.7	c.249+4386T>C		intron_variant		1	NM_003483.6	P1

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33566 AN: 152064 Hom.: 7845 Cov.: 32

Gnomad AFR AF: 0.588

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.0648

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.0694

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0469

Gnomad OTH AF: 0.184

GnomAD4 exome AF: 0.0726 AC: 58968 AN: 812006 Hom.: 5967 Cov.: 11 AF XY: 0.0721 AC XY: 27516 AN XY: 381656

Gnomad4 AFR exome AF: 0.627

Gnomad4 AMR exome AF: 0.145

Gnomad4 ASJ exome AF: 0.0635

Gnomad4 EAS exome AF: 0.232

Gnomad4 SAS exome AF: 0.254

Gnomad4 FIN exome AF: 0.0648

Gnomad4 NFE exome AF: 0.0477

Gnomad4 OTH exome AF: 0.119

GnomAD4 genome AF: 0.221 AC: 33652 AN: 152182 Hom.: 7873 Cov.: 32 AF XY: 0.221 AC XY: 16439 AN XY: 74410

Gnomad4 AFR AF: 0.588

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.0648

Gnomad4 EAS AF: 0.235

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.0694

Gnomad4 NFE AF: 0.0468

Gnomad4 OTH AF: 0.191

Alfa AF: 0.0801 Hom.: 1744

Bravo AF: 0.241

Asia WGS AF: 0.302 AC: 1050 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.2
DANN	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2272047; hg19: chr12-66236735;