rs2612060

chr12-65849722-A-Gchr12-65849722-A-T

Variant summary

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

The NM_003483.6(HMGA2):c.249+11153A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0701 in 142,664 control chromosomes in the GnomAD database, including 400 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 0.070 (400 hom., cov: 31)
• Consequence: HMGA2 NM_003483.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMGA2	NM_003483.6	c.249+11153A>G		intron_variant		ENST00000403681.7
HMGA2	NM_001300918.1	c.249+11153A>G		intron_variant
HMGA2	NM_001300919.1	c.249+11153A>G		intron_variant
HMGA2	NM_003484.1	c.249+11153A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMGA2	ENST00000403681.7	c.249+11153A>G		intron_variant		1	NM_003483.6	P1

Frequencies

GnomAD3 genomes AF: 0.0702 AC: 10006 AN: 142626 Hom.: 401 Cov.: 31

Gnomad AFR AF: 0.0496

Gnomad AMI AF: 0.0835

Gnomad AMR AF: 0.0622

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.0475

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0751

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.0701 AC: 10004 AN: 142664 Hom.: 400 Cov.: 31 AF XY: 0.0714 AC XY: 4955 AN XY: 69378

Gnomad4 AFR AF: 0.0496

Gnomad4 AMR AF: 0.0621

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.0475

Gnomad4 NFE AF: 0.0751

Gnomad4 OTH AF: 0.101

Alfa AF: 0.0753 Hom.: 625

Bravo AF: 0.0672

Asia WGS AF: 0.108 AC: 375 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.036
Dann	Benign	0.52

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: rs2612060; hg19: chr12-66243502;