dbSNP rs17179670: HMGA2:c.*4599A>G (chr12-65956032-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000541363.5(HMGA2):c.*4599A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,054 control chromosomes in the GnomAD database, including 2,506 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 0.16 ( 2505 hom., cov: 32)

Exomes 𝑓: 0.33 ( 1 hom. )

Consequence

HMGA2
ENST00000541363.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.281

Publications

5 publications found

Variant links:

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)

HMGA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMGA2	NM_003483.6 link	c.282+4617A>G		intron_variant	Intron 4 of 4	ENST00000403681.7	NP_003474.1	P52926-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
HMGA2	ENST00000541363.5 link	c.*4599A>G	3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000439317.1	F5H2U8
HMGA2	ENST00000403681.7 link	c.282+4617A>G	intron_variant	Intron 4 of 4	1	NM_003483.6	ENSP00000384026.2	P52926-1
HMGA2	ENST00000539662.1 link	n.*151+4617A>G	intron_variant	Intron 4 of 4	3		ENSP00000440919.1	H0YFY4

Frequencies

GnomAD3 genomes

AF:

0.161

AC:

24429

AN:

151930

Hom.:

2504

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0441

Gnomad AMI

AF:

0.248

Gnomad AMR

AF:

0.180

Gnomad ASJ

AF:

0.260

Gnomad EAS

AF:

0.0587

Gnomad SAS

AF:

0.317

Gnomad FIN

AF:

0.236

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.204

Gnomad OTH

AF:

0.203

GnomAD4 exome

AF:

0.333

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.161

AC:

24429

AN:

152048

Hom.:

2505

Cov.:

AF XY:

0.165

AC XY:

12277

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.0440

AC:

1826

AN:

41502

American (AMR)

AF:

0.180

AC:

2754

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.260

AC:

902

AN:

3468

East Asian (EAS)

AF:

0.0588

AC:

303

AN:

5152

South Asian (SAS)

AF:

0.319

AC:

1531

AN:

4796

European-Finnish (FIN)

AF:

0.236

AC:

2490

AN:

10556

Middle Eastern (MID)

AF:

0.289

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.204

AC:

13887

AN:

67976

Other (OTH)

AF:

0.201

AC:

425

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1005

2009

3014

4018

5023

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.190

Hom.:

3346

Bravo

AF:

0.150

Asia WGS

AF:

0.168

AC:

582

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

7.0

(source)

DANN

Benign

0.75

PhyloP100

0.28

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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rs17179670

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over