rs12998729

Variant names:

• chr2-147859723-G-A
• rs12998729
• NM_001616.5:c.55+14516G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001616.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACVR2A	NM_001616.5	MANE Select	c.55+14516G>A		intron	N/A	NP_001607.1
	ACVR2A	NM_001278579.2		c.55+14516G>A		intron	N/A	NP_001265508.1
	ACVR2A	NM_001278580.2		c.-207+15017G>A		intron	N/A	NP_001265509.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACVR2A	ENST00000241416.12	TSL:1 MANE Select	c.55+14516G>A		intron	N/A	ENSP00000241416.7
	ACVR2A	ENST00000404590.1	TSL:1	c.55+14516G>A		intron	N/A	ENSP00000384338.1
	ACVR2A	ENST00000535787.5	TSL:2	c.-207+15017G>A		intron	N/A	ENSP00000439988.1

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

African (AFR) AF: 0.181 AC: 7499 AN: 41346

American (AMR) AF: 0.318 AC: 4835 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1094 AN: 3462

East Asian (EAS) AF: 0.462 AC: 2371 AN: 5130

South Asian (SAS) AF: 0.291 AC: 1396 AN: 4800

European-Finnish (FIN) AF: 0.336 AC: 3524 AN: 10496

Middle Eastern (MID) AF: 0.387 AC: 113 AN: 292

European-Non Finnish (NFE) AF: 0.310 AC: 21018 AN: 67894

Other (OTH) AF: 0.310 AC: 652 AN: 2104

Alfa AF: 0.305 Hom.: 6537

Bravo AF: 0.281

Asia WGS AF: 0.317 AC: 1102 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.8
DANN	Benign	0.45
PhyloP100		0.017
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: rs12998729; hg19: chr2-148617292;