rs17179670

Positions:

• chr12-65956032-A-G

Variant summary

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

The ENST00000541363.5(HMGA2):​c.*4599A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,054 control chromosomes in the GnomAD database, including 2,506 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 0.16 (2505 hom., cov: 32)
  • Exomes 𝑓: 0.33 (1 hom.)
• Consequence: HMGA2 ENST00000541363.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.281

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 (SAS) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMGA2	NM_003483.6	c.282+4617A>G		intron_variant		ENST00000403681.7	NP_003474.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMGA2	ENST00000541363.5	c.*4599A>G		3_prime_UTR_variant	4/4	1		ENSP00000439317.1
HMGA2	ENST00000403681.7	c.282+4617A>G		intron_variant		1	NM_003483.6	ENSP00000384026.2
HMGA2	ENST00000539662.1	n.*151+4617A>G		intron_variant		3		ENSP00000440919.1

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24429 AN: 151930 Hom.: 2504 Cov.: 32

Gnomad AFR AF: 0.0441

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.0587

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.203

GnomAD4 exome AF: 0.333 AC: 2 AN: 6 Hom.: 1 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.161 AC: 24429 AN: 152048 Hom.: 2505 Cov.: 32 AF XY: 0.165 AC XY: 12277 AN XY: 74288

Gnomad4 AFR AF: 0.0440

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.260

Gnomad4 EAS AF: 0.0588

Gnomad4 SAS AF: 0.319

Gnomad4 FIN AF: 0.236

Gnomad4 NFE AF: 0.204

Gnomad4 OTH AF: 0.201

Alfa AF: 0.195 Hom.: 2555

Bravo AF: 0.150

Asia WGS AF: 0.168 AC: 582 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	0.75

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: rs17179670; hg19: chr12-66349812;