chr12-65950030-C-T

Position:

• chr12-65950030-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003483.6(HMGA2):​c.250-1353C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 151,950 control chromosomes in the GnomAD database, including 22,901 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.54 (22901 hom., cov: 32)
• Consequence: HMGA2 NM_003483.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMGA2	NM_003483.6	c.250-1353C>T		intron_variant		ENST00000403681.7	NP_003474.1
HMGA2	NM_001300918.1	c.250-1353C>T		intron_variant			NP_001287847.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMGA2	ENST00000403681.7	c.250-1353C>T		intron_variant		1	NM_003483.6	ENSP00000384026	P1
HMGA2	ENST00000541363.5	c.250-1353C>T		intron_variant		1		ENSP00000439317
HMGA2	ENST00000393577.7	c.250-1353C>T		intron_variant		3		ENSP00000377205
HMGA2	ENST00000539662.1	c.*119-1353C>T		intron_variant, NMD_transcript_variant		3		ENSP00000440919

Frequencies

GnomAD3 genomes AF: 0.540 AC: 82052 AN: 151832 Hom.: 22882 Cov.: 32

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.688

Gnomad EAS AF: 0.891

Gnomad SAS AF: 0.747

Gnomad FIN AF: 0.485

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.577

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.540 AC: 82108 AN: 151950 Hom.: 22901 Cov.: 32 AF XY: 0.548 AC XY: 40691 AN XY: 74284

Gnomad4 AFR AF: 0.501

Gnomad4 AMR AF: 0.613

Gnomad4 ASJ AF: 0.688

Gnomad4 EAS AF: 0.890

Gnomad4 SAS AF: 0.747

Gnomad4 FIN AF: 0.485

Gnomad4 NFE AF: 0.507

Gnomad4 OTH AF: 0.573

Alfa AF: 0.538 Hom.: 37275

Bravo AF: 0.553

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.5
DANN	Benign	0.76

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

Other links and lift over

dbSNP: rs10784502; hg19: chr12-66343810;