Variant 12-65952427-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The ENST00000403681.7(HMGA2):c.282+1012T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000445 in 1,534,460 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0025 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00022 ( 2 hom. )

Consequence

HMGA2
ENST00000403681.7 intron

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.54

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 12-65952427-T-C is Benign according to our data. Variant chr12-65952427-T-C is described in ClinVar as [Benign]. Clinvar id is 3055904.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 373 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMGA2	NM_003483.6 linkuse as main transcript	c.282+1012T>C		intron_variant		ENST00000403681.7	NP_003474.1
HMGA2	NM_001300918.1 linkuse as main transcript	c.354T>C	p.Thr118=	synonymous_variant	5/5		NP_001287847.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMGA2	ENST00000541363.5 linkuse as main transcript	c.*994T>C		3_prime_UTR_variant	4/4	1		ENSP00000439317
HMGA2	ENST00000403681.7 linkuse as main transcript	c.282+1012T>C		intron_variant		1	NM_003483.6	ENSP00000384026	P1	P52926-1
HMGA2	ENST00000393577.7 linkuse as main transcript	c.354T>C	p.Thr118=	synonymous_variant	5/5	3		ENSP00000377205
HMGA2	ENST00000539662.1 linkuse as main transcript	c.*151+1012T>C		intron_variant, NMD_transcript_variant		3		ENSP00000440919

Frequencies

GnomAD3 genomes

AF:

0.00246

AC:

374

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00850

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.000430

AC:

AN:

127928

Hom.:

AF XY:

0.000442

AC XY:

AN XY:

70062

show subpopulations

Gnomad AFR exome

AF:

0.00773

Gnomad AMR exome

AF:

0.000288

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000212

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000224

AC:

310

AN:

1382238

Hom.:

Cov.:

AF XY:

0.000205

AC XY:

140

AN XY:

682066

show subpopulations

Gnomad4 AFR exome

AF:

0.00722

Gnomad4 AMR exome

AF:

0.000700

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000379

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000186

Gnomad4 OTH exome

AF:

0.000588

GnomAD4 genome

AF:

0.00245

AC:

373

AN:

152222

Hom.:

Cov.:

AF XY:

0.00241

AC XY:

179

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.00843

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.00145

Hom.:

Bravo

AF:

0.00287

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

HMGA2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 23, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Benign

0.85

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

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