chr2-147899548-G-A

Variant names:

• chr2-147899548-G-A
• rs1128919
• NM_001616.5:c.354G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001616.5(ACVR2A):​c.354G>A​(p.Pro118Pro) 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
• Publications: 30 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]

ENSG00000223911 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.491 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACVR2A	NM_001616.5	MANE Select	c.354G>A	p.Pro118Pro	synonymous	Exon 3 of 11	NP_001607.1
	ACVR2A	NM_001278579.2		c.354G>A	p.Pro118Pro	synonymous	Exon 4 of 12	NP_001265508.1
	ACVR2A	NM_001278580.2		c.30G>A	p.Pro10Pro	synonymous	Exon 3 of 11	NP_001265509.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACVR2A	ENST00000241416.12	TSL:1 MANE Select	c.354G>A	p.Pro118Pro	synonymous	Exon 3 of 11	ENSP00000241416.7
	ACVR2A	ENST00000404590.1	TSL:1	c.354G>A	p.Pro118Pro	synonymous	Exon 4 of 12	ENSP00000384338.1
	ACVR2A	ENST00000943648.1		c.354G>A	p.Pro118Pro	synonymous	Exon 3 of 12	ENSP00000613707.1

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

GnomAD2 exomes AF: 0.354 AC: 88511 AN: 250214 AF XY: 0.348

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 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

African (AFR) AF: 0.297 AC: 9918 AN: 33404

American (AMR) AF: 0.452 AC: 20160 AN: 44580

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 8885 AN: 26084

East Asian (EAS) AF: 0.501 AC: 19869 AN: 39658

South Asian (SAS) AF: 0.316 AC: 27187 AN: 85970

European-Finnish (FIN) AF: 0.335 AC: 17892 AN: 53344

Middle Eastern (MID) AF: 0.436 AC: 2507 AN: 5752

European-Non Finnish (NFE) AF: 0.306 AC: 339836 AN: 1110370

Other (OTH) AF: 0.322 AC: 19433 AN: 60290

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

African (AFR) AF: 0.299 AC: 12377 AN: 41420

American (AMR) AF: 0.382 AC: 5818 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 1138 AN: 3466

East Asian (EAS) AF: 0.507 AC: 2615 AN: 5160

South Asian (SAS) AF: 0.311 AC: 1500 AN: 4822

European-Finnish (FIN) AF: 0.335 AC: 3521 AN: 10516

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.314 AC: 21322 AN: 67882

Other (OTH) AF: 0.347 AC: 733 AN: 2110

Alfa AF: 0.324 Hom.: 13847

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	12
DANN	Benign	0.76
PhyloP100		-0.67
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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