12-65966288-C-T

Variant names:

• chr12-65966288-C-T
• rs11175982
• NM_003483.6:c.*2996C>T

Variant summary

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

The NM_003483.6(HMGA2):​c.*2996C>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 0.224 in 185,090 control chromosomes in the GnomAD database, including 6,450 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 0.21 (4430 hom., cov: 32)
  • Exomes 𝑓: 0.30 (2020 hom.)
• Consequence: HMGA2 NM_003483.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18

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=-0.67).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMGA2	NM_003483.6	c.*2996C>T		3_prime_UTR_variant	Exon 5 of 5	ENST00000403681.7	NP_003474.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMGA2	ENST00000403681.7	c.*2996C>T		3_prime_UTR_variant	Exon 5 of 5	1	NM_003483.6	ENSP00000384026.2

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31698 AN: 151946 Hom.: 4433 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.751

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.217

GnomAD4 exome AF: 0.295 AC: 9747 AN: 33026 Hom.: 2020 Cov.: 0 AF XY: 0.287 AC XY: 4419 AN XY: 15388

Gnomad4 AFR exome AF: 0.155

Gnomad4 AMR exome AF: 0.339

Gnomad4 ASJ exome AF: 0.284

Gnomad4 EAS exome AF: 0.676

Gnomad4 SAS exome AF: 0.331

Gnomad4 FIN exome AF: 0.170

Gnomad4 NFE exome AF: 0.192

Gnomad4 OTH exome AF: 0.223

GnomAD4 genome AF: 0.208 AC: 31697 AN: 152064 Hom.: 4430 Cov.: 32 AF XY: 0.213 AC XY: 15849 AN XY: 74352

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.312

Gnomad4 ASJ AF: 0.264

Gnomad4 EAS AF: 0.750

Gnomad4 SAS AF: 0.293

Gnomad4 FIN AF: 0.158

Gnomad4 NFE AF: 0.183

Gnomad4 OTH AF: 0.216

Alfa AF: 0.202 Hom.: 1614

Bravo AF: 0.222

Asia WGS AF: 0.461 AC: 1599 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	7.0
DANN	Benign	0.72

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: rs11175982; hg19: chr12-66360068;