ENST00000536545.5:c.424C>T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PVS1_ModerateBP6_ModerateBS2

The ENST00000536545.5(HMGA2):c.424C>T(p.Arg142*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HMGA2
ENST00000536545.5 stop_gained

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.305

Publications

0 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: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
uterine corpus leiomyoma
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

HMGA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.045 CDS is truncated, and there are 0 pathogenic variants in the truncated region.

BP6

Variant 12-65914894-C-T is Benign according to our data. Variant chr12-65914894-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2643164.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome4 at 8 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000536545.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HMGA2	NM_003483.6	MANE Select	c.250-36489C>T		intron	N/A	NP_003474.1	P52926-1
HMGA2	NM_001300919.1		c.424C>T	p.Arg142*	stop_gained	Exon 4 of 4	NP_001287848.1	Q1M183
HMGA2	NM_001300918.1		c.250-36489C>T		intron	N/A	NP_001287847.1	F5H2A4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HMGA2	ENST00000536545.5	TSL:1	c.424C>T	p.Arg142*	stop_gained	Exon 4 of 4	ENSP00000437621.1	F5H6H0
HMGA2	ENST00000403681.7	TSL:1 MANE Select	c.250-36489C>T		intron	N/A	ENSP00000384026.2	P52926-1
HMGA2	ENST00000354636.7	TSL:1	c.250-165C>T		intron	N/A	ENSP00000346658.3	P52926-2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152108

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000241

AC:

AN:

207060

AF XY:

0.0000176

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000529

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000127

AC:

AN:

631732

Hom.:

Cov.:

AF XY:

0.0000178

AC XY:

AN XY:

336944

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

17100

American (AMR)

AF:

0.00

AC:

AN:

37674

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17348

East Asian (EAS)

AF:

0.00

AC:

AN:

30234

South Asian (SAS)

AF:

0.00

AC:

AN:

66480

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29448

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3266

European-Non Finnish (NFE)

AF:

0.0000175

AC:

AN:

399930

Other (OTH)

AF:

0.0000331

AC:

AN:

30252

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

152108

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74300

African (AFR)

AF:

0.00

AC:

AN:

41416

American (AMR)

AF:

0.00

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2086

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000248

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.92

CADD

Benign

2.4

(source)

DANN

Benign

0.88

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.0033

PhyloP100

0.30

Vest4

0.078

GERP RS

0.23

Mutation Taster

=191/9

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over