rs8756

Variant names:

• chr12-65965972-C-A
• rs8756
• NM_003483.6:c.*2680C>A

Your query was ambiguous. Multiple possible variants found:

• chr12-65965972-C-A
• chr12-65965972-C-G
• chr12-65965972-C-T

Variant summary

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

The NM_003483.6(HMGA2):​c.*2680C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 219,314 control chromosomes in the GnomAD database, including 37,923 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 0.57 (25410 hom., cov: 32)
  • Exomes 𝑓: 0.59 (12513 hom.)
• Consequence: HMGA2 NM_003483.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.60
• Publications: 78 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=-0.62).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMGA2	NM_003483.6	c.*2680C>A		3_prime_UTR_variant	Exon 5 of 5	ENST00000403681.7	NP_003474.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMGA2	ENST00000403681.7	c.*2680C>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_003483.6	ENSP00000384026.2

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86686 AN: 151812 Hom.: 25380 Cov.: 32

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.675

Gnomad EAS AF: 0.900

Gnomad SAS AF: 0.752

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.512

Gnomad OTH AF: 0.596

GnomAD4 exome AF: 0.594 AC: 40012 AN: 67384 Hom.: 12513 Cov.: 0 AF XY: 0.591 AC XY: 18496 AN XY: 31304

African (AFR) AF: 0.606 AC: 1898 AN: 3130

American (AMR) AF: 0.647 AC: 1296 AN: 2002

Ashkenazi Jewish (ASJ) AF: 0.660 AC: 2808 AN: 4256

East Asian (EAS) AF: 0.865 AC: 8488 AN: 9808

South Asian (SAS) AF: 0.784 AC: 444 AN: 566

European-Finnish (FIN) AF: 0.513 AC: 243 AN: 474

Middle Eastern (MID) AF: 0.664 AC: 280 AN: 422

European-Non Finnish (NFE) AF: 0.520 AC: 21437 AN: 41186

Other (OTH) AF: 0.563 AC: 3118 AN: 5540

GnomAD4 genome AF: 0.571 AC: 86756 AN: 151930 Hom.: 25410 Cov.: 32 AF XY: 0.577 AC XY: 42864 AN XY: 74224

African (AFR) AF: 0.594 AC: 24583 AN: 41410

American (AMR) AF: 0.628 AC: 9572 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.675 AC: 2338 AN: 3466

East Asian (EAS) AF: 0.899 AC: 4656 AN: 5178

South Asian (SAS) AF: 0.752 AC: 3621 AN: 4816

European-Finnish (FIN) AF: 0.504 AC: 5312 AN: 10544

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.512 AC: 34755 AN: 67946

Other (OTH) AF: 0.593 AC: 1253 AN: 2114

Alfa AF: 0.544 Hom.: 108956

Bravo AF: 0.586

Asia WGS AF: 0.768 AC: 2667 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	6.9
DANN	Benign	0.81
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8756; hg19: chr12-66359752;