rs2272047

Variant names:

• chr12-65842955-T-C
• rs2272047
• ENST00000393578.7:c.*341T>C

Your query was ambiguous. Multiple possible variants found:

• chr12-65842955-T-C
• chr12-65842955-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000393578.7(HMGA2):​c.*341T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0961 in 964,188 control chromosomes in the GnomAD database, including 13,840 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 0.22 (7873 hom., cov: 32)
  • Exomes 𝑓: 0.073 (5967 hom.)
• Consequence: HMGA2 ENST00000393578.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.290
• Publications: 11 publications found

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 Gene-Disease associations (from GenCC):

• Silver-Russell syndrome 5

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• uterine corpus leiomyoma

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000393578.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMGA2	NM_003483.6	MANE Select	c.249+4386T>C		intron	N/A	NP_003474.1
	HMGA2	NM_001330190.1		c.*341T>C		3_prime_UTR	Exon 4 of 4	NP_001317119.1
	HMGA2	NM_001300919.1		c.249+4386T>C		intron	N/A	NP_001287848.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMGA2	ENST00000393578.7	TSL:1	c.*341T>C		3_prime_UTR	Exon 4 of 4	ENSP00000377206.3
	HMGA2	ENST00000403681.7	TSL:1 MANE Select	c.249+4386T>C		intron	N/A	ENSP00000384026.2
	HMGA2	ENST00000536545.5	TSL:1	c.249+4386T>C		intron	N/A	ENSP00000437621.1

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33566 AN: 152064 Hom.: 7845 Cov.: 32

Gnomad AFR AF: 0.588

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.0648

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.0694

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0469

Gnomad OTH AF: 0.184

GnomAD4 exome AF: 0.0726 AC: 58968 AN: 812006 Hom.: 5967 Cov.: 11 AF XY: 0.0721 AC XY: 27516 AN XY: 381656

African (AFR) AF: 0.627 AC: 11672 AN: 18626

American (AMR) AF: 0.145 AC: 749 AN: 5174

Ashkenazi Jewish (ASJ) AF: 0.0635 AC: 675 AN: 10622

East Asian (EAS) AF: 0.232 AC: 3999 AN: 17266

South Asian (SAS) AF: 0.254 AC: 3887 AN: 15320

European-Finnish (FIN) AF: 0.0648 AC: 308 AN: 4754

Middle Eastern (MID) AF: 0.0986 AC: 200 AN: 2028

European-Non Finnish (NFE) AF: 0.0477 AC: 33657 AN: 706188

Other (OTH) AF: 0.119 AC: 3821 AN: 32028

GnomAD4 genome AF: 0.221 AC: 33652 AN: 152182 Hom.: 7873 Cov.: 32 AF XY: 0.221 AC XY: 16439 AN XY: 74410

African (AFR) AF: 0.588 AC: 24366 AN: 41470

American (AMR) AF: 0.147 AC: 2246 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0648 AC: 225 AN: 3470

East Asian (EAS) AF: 0.235 AC: 1221 AN: 5186

South Asian (SAS) AF: 0.254 AC: 1224 AN: 4822

European-Finnish (FIN) AF: 0.0694 AC: 736 AN: 10612

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.0468 AC: 3186 AN: 68016

Other (OTH) AF: 0.191 AC: 403 AN: 2114

Alfa AF: 0.0969 Hom.: 3295

Bravo AF: 0.241

Asia WGS AF: 0.302 AC: 1050 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.2
DANN	Benign	0.43
PhyloP100		0.29
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2272047; hg19: chr12-66236735;