12-65961131-G-A

Position:

• chr12-65961131-G-A

Variant summary

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

The NM_003483.6(HMGA2):​c.283-2114G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 152,032 control chromosomes in the GnomAD database, including 14,425 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 0.42 (14425 hom., cov: 33)
• Consequence: HMGA2 NM_003483.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.54

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMGA2	NM_003483.6	c.283-2114G>A		intron_variant		ENST00000403681.7	NP_003474.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMGA2	ENST00000403681.7	c.283-2114G>A		intron_variant		1	NM_003483.6	ENSP00000384026	P1
HMGA2	ENST00000539662.1	c.*152-2114G>A		intron_variant, NMD_transcript_variant		3		ENSP00000440919

Frequencies

GnomAD3 genomes AF: 0.422 AC: 64129 AN: 151912 Hom.: 14416 Cov.: 33

Gnomad AFR AF: 0.358

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.855

Gnomad SAS AF: 0.615

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.457

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

GnomAD4 genome AF: 0.422 AC: 64166 AN: 152032 Hom.: 14425 Cov.: 33 AF XY: 0.429 AC XY: 31885 AN XY: 74294

Gnomad4 AFR AF: 0.358

Gnomad4 AMR AF: 0.516

Gnomad4 ASJ AF: 0.518

Gnomad4 EAS AF: 0.855

Gnomad4 SAS AF: 0.615

Gnomad4 FIN AF: 0.394

Gnomad4 NFE AF: 0.391

Gnomad4 OTH AF: 0.454

Alfa AF: 0.419 Hom.: 20711

Bravo AF: 0.433

Asia WGS AF: 0.645 AC: 2238 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.011
DANN	Benign	0.54

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: rs867633; hg19: chr12-66354911;