dbSNP rs1128919: ACVR2A:p.Pro118Pro (chr2-147899548-G-A) – ACMG Classification: Benign (-8 pts)

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.673

Publications

30 publications found

Variant links:

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]

ACVR2A links:

ENSG00000223911 (HGNC:):

ENSG00000223911 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACVR2A	NM_001616.5 link	c.354G>A	p.Pro118Pro	synonymous_variant	Exon 3 of 11	ENST00000241416.12	NP_001607.1	P27037-1
ACVR2A	NM_001278579.2 link	c.354G>A	p.Pro118Pro	synonymous_variant	Exon 4 of 12		NP_001265508.1	P27037-1
ACVR2A	NM_001278580.2 link	c.30G>A	p.Pro10Pro	synonymous_variant	Exon 3 of 11		NP_001265509.1	P27037-2
ACVR2A	XM_047446292.1 link	c.30G>A	p.Pro10Pro	synonymous_variant	Exon 3 of 11		XP_047302248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACVR2A	ENST00000241416.12 link	c.354G>A	p.Pro118Pro	synonymous_variant	Exon 3 of 11	1	NM_001616.5	ENSP00000241416.7		P27037-1

Frequencies

GnomAD3 genomes

AF:

0.325

AC:

49345

AN:

151700

Hom.:

8268

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.318

AC XY:

231075

AN XY:

726038

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

14636

29272

43909

58545

73181

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11234

22468

33702

44936

56170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.325

AC:

49394

AN:

151818

Hom.:

8273

Cov.:

AF XY:

0.327

AC XY:

24271

AN XY:

74188

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1693

3387

5080

6774

8467

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

492

984

1476

1968

2460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

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)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over