NM_003483.6:c.249+3115T>C

Variant summary

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

The NM_003483.6(HMGA2):​c.249+3115T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0745 in 152,282 control chromosomes in the GnomAD database, including 476 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 0.075 ( 476 hom., cov: 32)

Consequence

HMGA2
NM_003483.6 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0110

Publications

8 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)

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=-0.82).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HMGA2NM_003483.6 linkc.249+3115T>C intron_variant Intron 3 of 4 ENST00000403681.7 NP_003474.1 P52926-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HMGA2ENST00000403681.7 linkc.249+3115T>C intron_variant Intron 3 of 4 1 NM_003483.6 ENSP00000384026.2 P52926-1

Frequencies

GnomAD3 genomes
AF:
0.0746
AC:
11351
AN:
152164
Hom.:
477
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0686
Gnomad AMI
AF:
0.0835
Gnomad AMR
AF:
0.0632
Gnomad ASJ
AF:
0.124
Gnomad EAS
AF:
0.102
Gnomad SAS
AF:
0.136
Gnomad FIN
AF:
0.0497
Gnomad MID
AF:
0.123
Gnomad NFE
AF:
0.0746
Gnomad OTH
AF:
0.101
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0745
AC:
11350
AN:
152282
Hom.:
476
Cov.:
32
AF XY:
0.0759
AC XY:
5654
AN XY:
74454
show subpopulations
African (AFR)
AF:
0.0685
AC:
2848
AN:
41554
American (AMR)
AF:
0.0631
AC:
966
AN:
15302
Ashkenazi Jewish (ASJ)
AF:
0.124
AC:
431
AN:
3470
East Asian (EAS)
AF:
0.103
AC:
532
AN:
5182
South Asian (SAS)
AF:
0.135
AC:
652
AN:
4820
European-Finnish (FIN)
AF:
0.0497
AC:
527
AN:
10612
Middle Eastern (MID)
AF:
0.112
AC:
33
AN:
294
European-Non Finnish (NFE)
AF:
0.0746
AC:
5073
AN:
68022
Other (OTH)
AF:
0.100
AC:
212
AN:
2116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
557
1113
1670
2226
2783
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
140
280
420
560
700
<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:
0.0652
Hom.:
56
Bravo
AF:
0.0745
Asia WGS
AF:
0.109
AC:
377
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
8.0
DANN
Benign
0.66
PhyloP100
0.011
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

Publications

Other links and lift over

dbSNP: rs2583937; hg19: chr12-66235464; API