rs17101839

Variant names:

• chr12-65851788-C-T
• rs17101839
• NM_003483.6:c.249+13219C>T

Variant summary

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

The ENST00000403681.7(HMGA2):​c.249+13219C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0746 in 292,012 control chromosomes in the GnomAD database, including 2,027 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 0.11 (1802 hom., cov: 32)
  • Exomes 𝑓: 0.041 (225 hom.)
• Consequence: HMGA2 ENST00000403681.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 4 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-AS1 (HGNC:53973): (HMGA2 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000403681.7. 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+13219C>T		intron	N/A	NP_003474.1
	HMGA2	NM_001300919.1		c.249+13219C>T		intron	N/A	NP_001287848.1
	HMGA2	NM_001300918.1		c.249+13219C>T		intron	N/A	NP_001287847.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMGA2	ENST00000403681.7	TSL:1 MANE Select	c.249+13219C>T		intron	N/A	ENSP00000384026.2
	HMGA2	ENST00000536545.5	TSL:1	c.249+13219C>T		intron	N/A	ENSP00000437621.1
	HMGA2	ENST00000354636.7	TSL:1	c.249+13219C>T		intron	N/A	ENSP00000346658.3

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15944 AN: 152112 Hom.: 1791 Cov.: 32

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0607

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0505

Gnomad FIN AF: 0.0212

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0322

Gnomad OTH AF: 0.0890

GnomAD4 exome AF: 0.0415 AC: 5799 AN: 139782 Hom.: 225 AF XY: 0.0429 AC XY: 3386 AN XY: 78872

African (AFR) AF: 0.243 AC: 615 AN: 2526

American (AMR) AF: 0.0297 AC: 268 AN: 9022

Ashkenazi Jewish (ASJ) AF: 0.0943 AC: 340 AN: 3606

East Asian (EAS) AF: 0.00 AC: 0 AN: 2528

South Asian (SAS) AF: 0.0553 AC: 1820 AN: 32920

European-Finnish (FIN) AF: 0.0254 AC: 187 AN: 7358

Middle Eastern (MID) AF: 0.0801 AC: 166 AN: 2072

European-Non Finnish (NFE) AF: 0.0285 AC: 2083 AN: 73084

Other (OTH) AF: 0.0480 AC: 320 AN: 6666

GnomAD4 genome AF: 0.105 AC: 15997 AN: 152230 Hom.: 1802 Cov.: 32 AF XY: 0.102 AC XY: 7627 AN XY: 74422

African (AFR) AF: 0.284 AC: 11786 AN: 41498

American (AMR) AF: 0.0606 AC: 927 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 410 AN: 3472

East Asian (EAS) AF: 0.000964 AC: 5 AN: 5186

South Asian (SAS) AF: 0.0497 AC: 240 AN: 4826

European-Finnish (FIN) AF: 0.0212 AC: 225 AN: 10594

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0322 AC: 2192 AN: 68030

Other (OTH) AF: 0.0885 AC: 187 AN: 2112

Alfa AF: 0.0830 Hom.: 202

Bravo AF: 0.116

Asia WGS AF: 0.0400 AC: 141 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.73
DANN	Benign	0.69
PhyloP100		-1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs17101839; hg19: chr12-66245568;