rs1042725

chr12-65964567-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.*1275C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 215,618 control chromosomes in the GnomAD database, including 29,032 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 0.49 (19233 hom., cov: 31)
  • Exomes 𝑓: 0.54 (9799 hom.)
• Consequence: HMGA2 NM_003483.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.508

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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMGA2	NM_003483.6	c.*1275C>T		3_prime_UTR_variant	5/5	ENST00000403681.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMGA2	ENST00000403681.7	c.*1275C>T		3_prime_UTR_variant	5/5	1	NM_003483.6	P1

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74760 AN: 151686 Hom.: 19238 Cov.: 31

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.588

Gnomad ASJ AF: 0.657

Gnomad EAS AF: 0.811

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.528

GnomAD4 exome AF: 0.543 AC: 34681 AN: 63814 Hom.: 9799 Cov.: 0 AF XY: 0.544 AC XY: 16165 AN XY: 29720

Gnomad4 AFR exome AF: 0.391

Gnomad4 AMR exome AF: 0.593

Gnomad4 ASJ exome AF: 0.644

Gnomad4 EAS exome AF: 0.729

Gnomad4 SAS exome AF: 0.713

Gnomad4 FIN exome AF: 0.502

Gnomad4 NFE exome AF: 0.499

Gnomad4 OTH exome AF: 0.521

GnomAD4 genome AF: 0.493 AC: 74774 AN: 151804 Hom.: 19233 Cov.: 31 AF XY: 0.500 AC XY: 37101 AN XY: 74192

Gnomad4 AFR AF: 0.384

Gnomad4 AMR AF: 0.587

Gnomad4 ASJ AF: 0.657

Gnomad4 EAS AF: 0.810

Gnomad4 SAS AF: 0.676

Gnomad4 FIN AF: 0.487

Gnomad4 NFE AF: 0.491

Gnomad4 OTH AF: 0.524

Alfa AF: 0.520 Hom.: 39151

Bravo AF: 0.499

Asia WGS AF: 0.680 AC: 2360 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	6.2
Dann	Benign	0.46
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: rs1042725; hg19: chr12-66358347; COSMIC: COSV67804157; COSMIC: COSV67804157;