12-65867144-A-G

Position:

• chr12-65867144-A-G

Variant summary

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

The NM_003483.6(HMGA2):​c.249+28575A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 152,142 control chromosomes in the GnomAD database, including 37,750 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 0.64 (37750 hom., cov: 32)
• Consequence: HMGA2 NM_003483.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0770

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]

HMGA2-AS1 (HGNC:53973): (HMGA2 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMGA2	NM_003483.6	c.249+28575A>G		intron_variant		ENST00000403681.7
HMGA2-AS1	NR_158985.1	n.609-190T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMGA2	ENST00000403681.7	c.249+28575A>G		intron_variant		1	NM_003483.6	P1
HMGA2-AS1	ENST00000439236.6	n.451-190T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.639 AC: 97129 AN: 152024 Hom.: 37746 Cov.: 32

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.916

Gnomad AMR AF: 0.752

Gnomad ASJ AF: 0.719

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.863

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.857

Gnomad OTH AF: 0.656

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

GnomAD4 genome AF: 0.638 AC: 97126 AN: 152142 Hom.: 37750 Cov.: 32 AF XY: 0.638 AC XY: 47444 AN XY: 74380

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.753

Gnomad4 ASJ AF: 0.719

Gnomad4 EAS AF: 0.667

Gnomad4 SAS AF: 0.571

Gnomad4 FIN AF: 0.863

Gnomad4 NFE AF: 0.857

Gnomad4 OTH AF: 0.651

Alfa AF: 0.803 Hom.: 48725

Bravo AF: 0.613

Asia WGS AF: 0.551 AC: 1920 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.3
DANN	Benign	0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs343087; hg19: chr12-66260924; COSMIC: COSV62285494;