rs2854603

Variant names:

• chr12-65831749-C-G
• rs2854603
• NM_003483.6:c.198+3662C>G

Your query was ambiguous. Multiple possible variants found:

• chr12-65831749-C-G
• chr12-65831749-C-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.198+3662C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0938 in 151,772 control chromosomes in the GnomAD database, including 716 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 0.094 (716 hom., cov: 32)
• Consequence: HMGA2 NM_003483.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.151
• Publications: 4 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMGA2	NM_003483.6	c.198+3662C>G		intron_variant	Intron 2 of 4	ENST00000403681.7	NP_003474.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMGA2	ENST00000403681.7	c.198+3662C>G		intron_variant	Intron 2 of 4	1	NM_003483.6	ENSP00000384026.2

Frequencies

GnomAD3 genomes AF: 0.0937 AC: 14205 AN: 151654 Hom.: 713 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.0835

Gnomad AMR AF: 0.0804

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.0532

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0841

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.0938 AC: 14234 AN: 151772 Hom.: 716 Cov.: 32 AF XY: 0.0951 AC XY: 7055 AN XY: 74218

African (AFR) AF: 0.113 AC: 4682 AN: 41492

American (AMR) AF: 0.0803 AC: 1225 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 473 AN: 3460

East Asian (EAS) AF: 0.104 AC: 538 AN: 5170

South Asian (SAS) AF: 0.146 AC: 704 AN: 4814

European-Finnish (FIN) AF: 0.0532 AC: 563 AN: 10580

Middle Eastern (MID) AF: 0.137 AC: 40 AN: 292

European-Non Finnish (NFE) AF: 0.0841 AC: 5691 AN: 67688

Other (OTH) AF: 0.115 AC: 242 AN: 2108

Alfa AF: 0.0277 Hom.: 17

Bravo AF: 0.0959

Asia WGS AF: 0.118 AC: 411 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.6
DANN	Benign	0.34
PhyloP100		0.15
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: rs2854603; hg19: chr12-66225529;