rs1563834

chr12-65904251-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.250-47132C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 152,148 control chromosomes in the GnomAD database, including 5,853 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 0.24 (5853 hom., cov: 32)
• Consequence: HMGA2 NM_003483.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.425

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMGA2	NM_003483.6	c.250-47132C>T		intron_variant		ENST00000403681.7
HMGA2	NM_001300918.1	c.250-47132C>T		intron_variant
HMGA2	NM_001300919.1	c.250-10469C>T		intron_variant
HMGA2	NM_003484.1	c.250-10808C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMGA2	ENST00000403681.7	c.250-47132C>T		intron_variant		1	NM_003483.6	P1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 37007 AN: 152030 Hom.: 5832 Cov.: 32

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.247

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.244 AC: 37064 AN: 152148 Hom.: 5853 Cov.: 32 AF XY: 0.246 AC XY: 18264 AN XY: 74392

Gnomad4 AFR AF: 0.441

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.276

Gnomad4 SAS AF: 0.368

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.254

Alfa AF: 0.186 Hom.: 1181

Bravo AF: 0.253

Asia WGS AF: 0.364 AC: 1261 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.7
Dann	Benign	0.76

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: rs1563834; hg19: chr12-66298031;