2-147900020-A-G

Position:

• chr2-147900020-A-G

Variant summary

Our verdict is Benign. Variant got -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

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 -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/exons	MANE	UniProt
ACVR2A	NM_001616.5	c.528+122A>G		intron_variant		ENST00000241416.12
ACVR2A	NM_001278579.2	c.528+122A>G		intron_variant
ACVR2A	NM_001278580.2	c.204+122A>G		intron_variant
ACVR2A	XM_047446292.1	c.204+122A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACVR2A	ENST00000241416.12	c.528+122A>G		intron_variant		1	NM_001616.5	P1
ACVR2A	ENST00000404590.1	c.528+122A>G		intron_variant		1		P1
	ENST00000402410.2	n.210+410T>C		intron_variant, non_coding_transcript_variant		3
ACVR2A	ENST00000535787.5	c.204+122A>G		intron_variant		2

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

Gnomad4 AFR exome AF: 0.228

Gnomad4 AMR exome AF: 0.492

Gnomad4 ASJ exome AF: 0.594

Gnomad4 EAS exome AF: 0.495

Gnomad4 SAS exome AF: 0.651

Gnomad4 FIN exome AF: 0.617

Gnomad4 NFE exome AF: 0.622

Gnomad4 OTH exome AF: 0.585

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

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.513

Gnomad4 ASJ AF: 0.607

Gnomad4 EAS AF: 0.485

Gnomad4 SAS AF: 0.661

Gnomad4 FIN AF: 0.628

Gnomad4 NFE AF: 0.610

Gnomad4 OTH AF: 0.486

Alfa AF: 0.575 Hom.: 23951

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2288190; hg19: chr2-148657589;