dbSNP rs10784502: HMGA2:c.250-1353C>T (chr12-65950030-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_003483.6(HMGA2):c.250-1353C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 151,950 control chromosomes in the GnomAD database, including 22,901 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 0.54 ( 22901 hom., cov: 32)

Consequence

HMGA2
NM_003483.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0330

Publications

52 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=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMGA2	NM_003483.6 link	c.250-1353C>T		intron_variant	Intron 3 of 4	ENST00000403681.7	NP_003474.1	P52926-1
HMGA2	NM_001300918.1 link	c.250-1353C>T		intron_variant	Intron 3 of 4		NP_001287847.1	F5H2A4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
HMGA2	ENST00000403681.7 link	c.250-1353C>T	intron_variant	Intron 3 of 4	1	NM_003483.6	ENSP00000384026.2	P52926-1
HMGA2	ENST00000541363.5 link	c.250-1353C>T	intron_variant	Intron 3 of 3	1		ENSP00000439317.1	F5H2U8
HMGA2	ENST00000393577.7 link	c.250-1353C>T	intron_variant	Intron 3 of 4	3		ENSP00000377205.3	F5H2A4
HMGA2	ENST00000539662.1 link	n.*119-1353C>T	intron_variant	Intron 3 of 4	3		ENSP00000440919.1	H0YFY4

Frequencies

GnomAD3 genomes

AF:

0.540

AC:

82052

AN:

151832

Hom.:

22882

Cov.:

show subpopulations

Gnomad AFR

AF:

0.500

Gnomad AMI

AF:

0.529

Gnomad AMR

AF:

0.614

Gnomad ASJ

AF:

0.688

Gnomad EAS

AF:

0.891

Gnomad SAS

AF:

0.747

Gnomad FIN

AF:

0.485

Gnomad MID

AF:

0.630

Gnomad NFE

AF:

0.507

Gnomad OTH

AF:

0.577

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

GnomAD4 genome

AF:

0.540

AC:

82108

AN:

151950

Hom.:

22901

Cov.:

AF XY:

0.548

AC XY:

40691

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.501

AC:

20749

AN:

41442

American (AMR)

AF:

0.613

AC:

9362

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.688

AC:

2387

AN:

3472

East Asian (EAS)

AF:

0.890

AC:

4602

AN:

5168

South Asian (SAS)

AF:

0.747

AC:

3595

AN:

4814

European-Finnish (FIN)

AF:

0.485

AC:

5116

AN:

10546

Middle Eastern (MID)

AF:

0.626

AC:

184

AN:

294

European-Non Finnish (NFE)

AF:

0.507

AC:

34427

AN:

67942

Other (OTH)

AF:

0.573

AC:

1207

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

1913

3825

5738

7650

9563

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

716

1432

2148

2864

3580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.530

Hom.:

82119

Bravo

AF:

0.553

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.5

(source)

DANN

Benign

0.76

PhyloP100

-0.033

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over