rs12998729

Positions:

• chr2-147859723-G-A
• chr2-147859723-G-C

Variant summary

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

The NM_001616.5(ACVR2A):​c.55+14516G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 151,640 control chromosomes in the GnomAD database, including 6,452 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 0.28 (6452 hom., cov: 30)
• Consequence: ACVR2A NM_001616.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0170

Genes affected

ACVR2A (HGNC:173): (activin A receptor type 2A) This gene encodes a receptor that mediates the functions of activins, which are members of the transforming growth factor-beta (TGF-beta) superfamily involved in diverse biological processes. The encoded protein is a transmembrane serine-threonine kinase receptor which mediates signaling by forming heterodimeric complexes with various combinations of type I and type II receptors and ligands in a cell-specific manner. The encoded type II receptor is primarily involved in ligand-binding and includes an extracellular ligand-binding domain, a transmembrane domain and a cytoplasmic serine-threonine kinase domain. This gene may be associated with susceptibility to preeclampsia, a pregnancy-related disease which can result in maternal and fetal morbidity and mortality. Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, Jun 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACVR2A	NM_001616.5	c.55+14516G>A		intron_variant		ENST00000241416.12	NP_001607.1
ACVR2A	NM_001278579.2	c.55+14516G>A		intron_variant			NP_001265508.1
ACVR2A	NM_001278580.2	c.-207+15017G>A		intron_variant			NP_001265509.1
ACVR2A	XM_047446292.1	c.-270+15017G>A		intron_variant			XP_047302248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACVR2A	ENST00000241416.12	c.55+14516G>A		intron_variant		1	NM_001616.5	ENSP00000241416	P1

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42711 AN: 151524 Hom.: 6451 Cov.: 30

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.462

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.310

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

GnomAD4 genome AF: 0.282 AC: 42752 AN: 151640 Hom.: 6452 Cov.: 30 AF XY: 0.283 AC XY: 20995 AN XY: 74104

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.318

Gnomad4 ASJ AF: 0.316

Gnomad4 EAS AF: 0.462

Gnomad4 SAS AF: 0.291

Gnomad4 FIN AF: 0.336

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.310

Alfa AF: 0.308 Hom.: 5662

Bravo AF: 0.281

Asia WGS AF: 0.317 AC: 1102 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.8
DANN	Benign	0.45

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: rs12998729; hg19: chr2-148617292;