2-147900020-A-G

Variant names:

• chr2-147900020-A-G
• rs2288190
• NM_001616.5:c.528+122A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001616.5(ACVR2A):​c.528+122A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 1,135,974 control chromosomes in the GnomAD database, including 204,465 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 0.50 (20916 hom., cov: 32)
  • Exomes 𝑓: 0.61 (183549 hom.)
• Consequence: ACVR2A NM_001616.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.00
• Publications: 10 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACVR2A	NM_001616.5	c.528+122A>G		intron_variant	Intron 4 of 10	ENST00000241416.12	NP_001607.1
ACVR2A	NM_001278579.2	c.528+122A>G		intron_variant	Intron 5 of 11		NP_001265508.1
ACVR2A	NM_001278580.2	c.204+122A>G		intron_variant	Intron 4 of 10		NP_001265509.1
ACVR2A	XM_047446292.1	c.204+122A>G		intron_variant	Intron 4 of 10		XP_047302248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACVR2A	ENST00000241416.12	c.528+122A>G		intron_variant	Intron 4 of 10	1	NM_001616.5	ENSP00000241416.7

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75684 AN: 151818 Hom.: 20911 Cov.: 32

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.640

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.660

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.483

GnomAD4 exome AF: 0.605 AC: 595359 AN: 984038 Hom.: 183549 AF XY: 0.607 AC XY: 299193 AN XY: 492562

African (AFR) AF: 0.228 AC: 4922 AN: 21544

American (AMR) AF: 0.492 AC: 10805 AN: 21982

Ashkenazi Jewish (ASJ) AF: 0.594 AC: 10350 AN: 17424

East Asian (EAS) AF: 0.495 AC: 16686 AN: 33698

South Asian (SAS) AF: 0.651 AC: 37359 AN: 57354

European-Finnish (FIN) AF: 0.617 AC: 24745 AN: 40084

Middle Eastern (MID) AF: 0.463 AC: 1961 AN: 4240

European-Non Finnish (NFE) AF: 0.622 AC: 463141 AN: 744294

Other (OTH) AF: 0.585 AC: 25390 AN: 43418

GnomAD4 genome AF: 0.498 AC: 75712 AN: 151936 Hom.: 20916 Cov.: 32 AF XY: 0.504 AC XY: 37419 AN XY: 74264

African (AFR) AF: 0.248 AC: 10287 AN: 41482

American (AMR) AF: 0.513 AC: 7820 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.607 AC: 2107 AN: 3472

East Asian (EAS) AF: 0.485 AC: 2502 AN: 5160

South Asian (SAS) AF: 0.661 AC: 3181 AN: 4816

European-Finnish (FIN) AF: 0.628 AC: 6631 AN: 10562

Middle Eastern (MID) AF: 0.441 AC: 128 AN: 290

European-Non Finnish (NFE) AF: 0.610 AC: 41445 AN: 67896

Other (OTH) AF: 0.486 AC: 1027 AN: 2112

Alfa AF: 0.561 Hom.: 30631

Bravo AF: 0.470

Asia WGS AF: 0.598 AC: 2077 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	7.9
DANN	Benign	0.84
PhyloP100		1.0
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: rs2288190; hg19: chr2-148657589;