Variant chr12-65915116-A-G 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_003484.1(HMGA2):c.307A>G(p.Lys103Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00337 in 1,613,748 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0034 ( 10 hom. )

Consequence

HMGA2
NM_003484.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.467

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037813485).

BP6

Variant 12-65915116-A-G is Benign according to our data. Variant chr12-65915116-A-G is described in ClinVar as [Benign]. Clinvar id is 3044402.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 413 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMGA2	NM_003483.6 linkuse as main transcript	c.250-36267A>G		intron_variant		ENST00000403681.7	NP_003474.1	P52926-1
HMGA2	NM_003484.1 linkuse as main transcript	c.307A>G	p.Lys103Glu	missense_variant	4/4		NP_003475.1	P52926-2
HMGA2	NM_001300919.1 linkuse as main transcript	c.*202A>G		3_prime_UTR_variant	4/4		NP_001287848.1	Q1M183F5H6H0
HMGA2	NM_001300918.1 linkuse as main transcript	c.250-36267A>G		intron_variant			NP_001287847.1	F5H2A4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMGA2	ENST00000403681.7 linkuse as main transcript	c.250-36267A>G		intron_variant		1	NM_003483.6	ENSP00000384026.2		P52926-1

Frequencies

GnomAD3 genomes

AF:

0.00271

AC:

413

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000748

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00800

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00409

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.00304

AC:

763

AN:

251342

Hom.:

AF XY:

0.00286

AC XY:

389

AN XY:

135822

show subpopulations

Gnomad AFR exome

AF:

0.000615

Gnomad AMR exome

AF:

0.000868

Gnomad ASJ exome

AF:

0.000198

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0101

Gnomad NFE exome

AF:

0.00428

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00344

AC:

5025

AN:

1461402

Hom.:

Cov.:

AF XY:

0.00327

AC XY:

2375

AN XY:

727038

show subpopulations

Gnomad4 AFR exome

AF:

0.000717

Gnomad4 AMR exome

AF:

0.000693

Gnomad4 ASJ exome

AF:

0.000230

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0105

Gnomad4 NFE exome

AF:

0.00383

Gnomad4 OTH exome

AF:

0.00249

GnomAD4 genome

AF:

0.00271

AC:

413

AN:

152346

Hom.:

Cov.:

AF XY:

0.00285

AC XY:

212

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.000746

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00800

Gnomad4 NFE

AF:

0.00409

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.00346

Hom.:

Bravo

AF:

0.00203

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00389

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00337

AC:

ExAC

AF:

0.00275

AC:

334

EpiCase

AF:

0.00327

EpiControl

AF:

0.00326

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2024

HMGA2: PP2, BP4, BS1, BS2 -

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_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.65

CADD

Benign

1.1

DANN

Benign

0.47

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.40

M_CAP

Benign

0.0055

MetaRNN

Benign

0.0038

MetaSVM

Benign

-1.0

PROVEAN

Benign

1.4

REVEL

Benign

0.040

Sift

Pathogenic

0.0

Sift4G

Benign

0.53

Vest4

0.086

MVP

0.043

ClinPred

0.0082

GERP RS

-4.4

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