rs2612060

Variant names:

• chr12-65849722-A-G
• rs2612060
• NM_003483.6:c.249+11153A>G

Your query was ambiguous. Multiple possible variants found:

• chr12-65849722-A-G
• chr12-65849722-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003483.6(HMGA2):​c.249+11153A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0701 in 142,664 control chromosomes in the GnomAD database, including 400 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 0.070 (400 hom., cov: 31)
• Consequence: HMGA2 NM_003483.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46
• Publications: 11 publications found

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: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• uterine corpus leiomyoma

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMGA2	NM_003483.6	c.249+11153A>G		intron_variant	Intron 3 of 4	ENST00000403681.7	NP_003474.1
HMGA2	NM_001300919.1	c.249+11153A>G		intron_variant	Intron 3 of 3		NP_001287848.1
HMGA2	NM_001300918.1	c.249+11153A>G		intron_variant	Intron 3 of 4		NP_001287847.1
HMGA2	NM_003484.1	c.249+11153A>G		intron_variant	Intron 3 of 3		NP_003475.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMGA2	ENST00000403681.7	c.249+11153A>G		intron_variant	Intron 3 of 4	1	NM_003483.6	ENSP00000384026.2

Frequencies

GnomAD3 genomes AF: 0.0702 AC: 10006 AN: 142626 Hom.: 401 Cov.: 31

Gnomad AFR AF: 0.0496

Gnomad AMI AF: 0.0835

Gnomad AMR AF: 0.0622

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.0475

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0751

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.0701 AC: 10004 AN: 142664 Hom.: 400 Cov.: 31 AF XY: 0.0714 AC XY: 4955 AN XY: 69378

African (AFR) AF: 0.0496 AC: 1766 AN: 35598

American (AMR) AF: 0.0621 AC: 904 AN: 14564

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 415 AN: 3382

East Asian (EAS) AF: 0.102 AC: 501 AN: 4930

South Asian (SAS) AF: 0.141 AC: 626 AN: 4448

European-Finnish (FIN) AF: 0.0475 AC: 458 AN: 9632

Middle Eastern (MID) AF: 0.115 AC: 32 AN: 278

European-Non Finnish (NFE) AF: 0.0751 AC: 5024 AN: 66926

Other (OTH) AF: 0.101 AC: 202 AN: 1996

Alfa AF: 0.0743 Hom.: 757

Bravo AF: 0.0672

Asia WGS AF: 0.108 AC: 375 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.036
DANN	Benign	0.52
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2612060; hg19: chr12-66243502;