rs2272046

chr12-65830681-A-C

Variant summary

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

The NM_003483.6(HMGA2):c.198+2594A>C variant causes a intron change. The variant allele was found at a frequency of 0.0221 in 152,030 control chromosomes in the GnomAD database, including 61 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 0.022 (61 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HMGA2 NM_003483.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.17

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=-0.51).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMGA2	NM_003483.6	c.198+2594A>C		intron_variant		ENST00000403681.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMGA2	ENST00000403681.7	c.198+2594A>C		intron_variant		1	NM_003483.6	P1

Frequencies

GnomAD3 genomes AF: 0.0220 AC: 3343 AN: 151912 Hom.: 54 Cov.: 32

Gnomad AFR AF: 0.00415

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0188

Gnomad ASJ AF: 0.0271

Gnomad EAS AF: 0.0920

Gnomad SAS AF: 0.0263

Gnomad FIN AF: 0.0419

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0247

Gnomad OTH AF: 0.0263

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0221 AC: 3359 AN: 152030 Hom.: 61 Cov.: 32 AF XY: 0.0230 AC XY: 1708 AN XY: 74322

Gnomad4 AFR AF: 0.00414

Gnomad4 AMR AF: 0.0188

Gnomad4 ASJ AF: 0.0271

Gnomad4 EAS AF: 0.0926

Gnomad4 SAS AF: 0.0262

Gnomad4 FIN AF: 0.0419

Gnomad4 NFE AF: 0.0247

Gnomad4 OTH AF: 0.0336

Alfa AF: 0.0194 Hom.: 8

Bravo AF: 0.0197

Asia WGS AF: 0.0820 AC: 284 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
Cadd	Benign	20
Dann	Benign	0.75

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: rs2272046; hg19: chr12-66224461;