Variant 12-65952348-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001300918.1(HMGA2):c.283-8T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00819 in 1,533,102 control chromosomes in the GnomAD database, including 68 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0080 ( 16 hom., cov: 32)

Exomes 𝑓: 0.0082 ( 52 hom. )

Consequence

HMGA2
NM_001300918.1 splice_region, intron

Scores

Splicing: ADA: 0.00006732

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.300

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 12-65952348-T-C is Benign according to our data. Variant chr12-65952348-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2578687.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 1221 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMGA2	NM_003483.6 linkuse as main transcript	c.282+933T>C		intron_variant		ENST00000403681.7	NP_003474.1	P52926-1
HMGA2	NM_001300918.1 linkuse as main transcript	c.283-8T>C		splice_region_variant, intron_variant			NP_001287847.1	F5H2A4

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HMGA2	ENST00000541363.5 linkuse as main transcript	c.*915T>C	3_prime_UTR_variant	4/4	1		ENSP00000439317.1	F5H2U8
HMGA2	ENST00000403681.7 linkuse as main transcript	c.282+933T>C	intron_variant		1	NM_003483.6	ENSP00000384026.2	P52926-1
HMGA2	ENST00000393577.7 linkuse as main transcript	c.283-8T>C	splice_region_variant, intron_variant		3		ENSP00000377205.3	F5H2A4
HMGA2	ENST00000539662.1 linkuse as main transcript	n.*151+933T>C	intron_variant		3		ENSP00000440919.1	H0YFY4

Frequencies

GnomAD3 genomes

AF:

0.00802

AC:

1221

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00142

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00255

Gnomad ASJ

AF:

0.00663

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.0393

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00976

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00592

AC:

757

AN:

127864

Hom.:

AF XY:

0.00598

AC XY:

419

AN XY:

70022

show subpopulations

Gnomad AFR exome

AF:

0.000986

Gnomad AMR exome

AF:

0.00156

Gnomad ASJ exome

AF:

0.00630

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00251

Gnomad FIN exome

AF:

0.0344

Gnomad NFE exome

AF:

0.00843

Gnomad OTH exome

AF:

0.00577

GnomAD4 exome

AF:

0.00821

AC:

11338

AN:

1380820

Hom.:

Cov.:

AF XY:

0.00810

AC XY:

5519

AN XY:

681488

show subpopulations

Gnomad4 AFR exome

AF:

0.00124

Gnomad4 AMR exome

AF:

0.00165

Gnomad4 ASJ exome

AF:

0.00628

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00229

Gnomad4 FIN exome

AF:

0.0338

Gnomad4 NFE exome

AF:

0.00868

Gnomad4 OTH exome

AF:

0.00736

GnomAD4 genome

AF:

0.00802

AC:

1221

AN:

152282

Hom.:

Cov.:

AF XY:

0.00905

AC XY:

674

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00142

Gnomad4 AMR

AF:

0.00255

Gnomad4 ASJ

AF:

0.00663

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.0393

Gnomad4 NFE

AF:

0.00976

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.00953

Hom.:

Bravo

AF:

0.00461

Asia WGS

AF:

0.00173

AC:

AN:

3474

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2024

HMGA2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.8

DANN

Benign

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000067

dbscSNV1_RF

Benign

0.024

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over