chr12-65966384-C-T

Variant summary

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

The NM_003483.6(HMGA2):​c.*3092C>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 173,088 control chromosomes in the GnomAD database, including 22,691 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 0.49 ( 19260 hom., cov: 32)
Exomes 𝑓: 0.56 ( 3431 hom. )

Consequence

HMGA2
NM_003483.6 downstream_gene

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.789

Publications

34 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=-0.81).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HMGA2NM_003483.6 linkc.*3092C>T downstream_gene_variant ENST00000403681.7 NP_003474.1 P52926-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HMGA2ENST00000403681.7 linkc.*3092C>T downstream_gene_variant 1 NM_003483.6 ENSP00000384026.2 P52926-1

Frequencies

GnomAD3 genomes
AF:
0.493
AC:
74826
AN:
151916
Hom.:
19265
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.384
Gnomad AMI
AF:
0.529
Gnomad AMR
AF:
0.588
Gnomad ASJ
AF:
0.655
Gnomad EAS
AF:
0.810
Gnomad SAS
AF:
0.676
Gnomad FIN
AF:
0.486
Gnomad MID
AF:
0.570
Gnomad NFE
AF:
0.491
Gnomad OTH
AF:
0.527
GnomAD4 exome
AF:
0.560
AC:
11783
AN:
21054
Hom.:
3431
AF XY:
0.561
AC XY:
5492
AN XY:
9788
show subpopulations
African (AFR)
AF:
0.391
AC:
266
AN:
680
American (AMR)
AF:
0.557
AC:
244
AN:
438
Ashkenazi Jewish (ASJ)
AF:
0.640
AC:
853
AN:
1332
East Asian (EAS)
AF:
0.731
AC:
3104
AN:
4248
South Asian (SAS)
AF:
0.713
AC:
114
AN:
160
European-Finnish (FIN)
AF:
0.498
AC:
211
AN:
424
Middle Eastern (MID)
AF:
0.577
AC:
82
AN:
142
European-Non Finnish (NFE)
AF:
0.505
AC:
6051
AN:
11972
Other (OTH)
AF:
0.517
AC:
858
AN:
1658
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
234
467
701
934
1168
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
46
92
138
184
230
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.492
AC:
74840
AN:
152034
Hom.:
19260
Cov.:
32
AF XY:
0.500
AC XY:
37122
AN XY:
74302
show subpopulations
African (AFR)
AF:
0.384
AC:
15899
AN:
41454
American (AMR)
AF:
0.587
AC:
8970
AN:
15274
Ashkenazi Jewish (ASJ)
AF:
0.655
AC:
2273
AN:
3470
East Asian (EAS)
AF:
0.809
AC:
4183
AN:
5170
South Asian (SAS)
AF:
0.676
AC:
3258
AN:
4820
European-Finnish (FIN)
AF:
0.486
AC:
5140
AN:
10566
Middle Eastern (MID)
AF:
0.558
AC:
164
AN:
294
European-Non Finnish (NFE)
AF:
0.491
AC:
33368
AN:
67968
Other (OTH)
AF:
0.524
AC:
1104
AN:
2108
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
1881
3761
5642
7522
9403
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
674
1348
2022
2696
3370
<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:
0.490
Hom.:
30822
Bravo
AF:
0.499
Asia WGS
AF:
0.679
AC:
2358
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
0.91
DANN
Benign
0.67
PhyloP100
-0.79
Mutation Taster
=100/0
polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs7970350; hg19: chr12-66360164; API