rs1128919

chr2-147899548-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001616.5(ACVR2A):c.354G>A(p.Pro118=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 1,611,270 control chromosomes in the GnomAD database, including 84,561 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 0.33 (8273 hom., cov: 31)
  • Exomes 𝑓: 0.32 (76288 hom.)
• Consequence: ACVR2A NM_001616.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.673

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACVR2A	NM_001616.5	c.354G>A	p.Pro118=	synonymous_variant	3/11	ENST00000241416.12
ACVR2A	NM_001278579.2	c.354G>A	p.Pro118=	synonymous_variant	4/12
ACVR2A	NM_001278580.2	c.30G>A	p.Pro10=	synonymous_variant	3/11
ACVR2A	XM_047446292.1	c.30G>A	p.Pro10=	synonymous_variant	3/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACVR2A	ENST00000241416.12	c.354G>A	p.Pro118=	synonymous_variant	3/11	1	NM_001616.5	P1
	ENST00000402410.2	n.265C>T		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49345 AN: 151700 Hom.: 8268 Cov.: 31

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.349

GnomAD3 exomes AF: 0.354 AC: 88511 AN: 250214 Hom.: 16400 AF XY: 0.348 AC XY: 47125 AN XY: 135380

Gnomad AFR exome AF: 0.305

Gnomad AMR exome AF: 0.459

Gnomad ASJ exome AF: 0.346

Gnomad EAS exome AF: 0.521

Gnomad SAS exome AF: 0.310

Gnomad FIN exome AF: 0.332

Gnomad NFE exome AF: 0.318

Gnomad OTH exome AF: 0.350

GnomAD4 exome AF: 0.319 AC: 465687 AN: 1459452 Hom.: 76288 Cov.: 32 AF XY: 0.318 AC XY: 231075 AN XY: 726038

Gnomad4 AFR exome AF: 0.297

Gnomad4 AMR exome AF: 0.452

Gnomad4 ASJ exome AF: 0.341

Gnomad4 EAS exome AF: 0.501

Gnomad4 SAS exome AF: 0.316

Gnomad4 FIN exome AF: 0.335

Gnomad4 NFE exome AF: 0.306

Gnomad4 OTH exome AF: 0.322

GnomAD4 genome AF: 0.325 AC: 49394 AN: 151818 Hom.: 8273 Cov.: 31 AF XY: 0.327 AC XY: 24271 AN XY: 74188

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.382

Gnomad4 ASJ AF: 0.328

Gnomad4 EAS AF: 0.507

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.335

Gnomad4 NFE AF: 0.314

Gnomad4 OTH AF: 0.347

Alfa AF: 0.322 Hom.: 9798

Bravo AF: 0.333

Asia WGS AF: 0.349 AC: 1215 AN: 3476

EpiCase AF: 0.330

EpiControl AF: 0.332

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
Cadd	Benign	12
Dann	Benign	0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.36		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.36		Position offset: 19

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1128919; hg19: chr2-148657117; COSMIC: COSV54020221; COSMIC: COSV54020221;