Variant 12-65825285-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_003483.6(HMGA2):c.15T>G(p.Gly5=) variant causes a synonymous 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: 31)

Exomes 𝑓: 0.00044 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HMGA2
NM_003483.6 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.25

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:

RPSAP52 (HGNC:35752): (ribosomal protein SA pseudogene 52)

RPSAP52 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 12-65825285-T-G is Benign according to our data. Variant chr12-65825285-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 3033836.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.25 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMGA2	NM_003483.6 linkuse as main transcript	c.15T>G	p.Gly5=	synonymous_variant	1/5	ENST00000403681.7
RPSAP52	NR_026825.2 linkuse as main transcript	n.132+1558A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMGA2	ENST00000403681.7 linkuse as main transcript	c.15T>G	p.Gly5=	synonymous_variant	1/5	1	NM_003483.6	P1	P52926-1
RPSAP52	ENST00000489520.2 linkuse as main transcript	n.132+1558A>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151846

Hom.:

Cov.:

FAILED QC

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

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000441

AC:

605

AN:

1373382

Hom.:

Cov.:

AF XY:

0.000384

AC XY:

260

AN XY:

677756

show subpopulations

Gnomad4 AFR exome

AF:

0.000332

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000807

Gnomad4 EAS exome

AF:

0.0000286

Gnomad4 SAS exome

AF:

0.0000894

Gnomad4 FIN exome

AF:

0.0000531

Gnomad4 NFE exome

AF:

0.000526

Gnomad4 OTH exome

AF:

0.000314

GnomAD4 genome

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

AF:

0.00

AC:

AN:

151846

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74150

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

HMGA2-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 10, 2019

This variant is classified as likely 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

-0.80

Cadd

Benign

8.6

Dann

Benign

0.42

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over