rs3768688

Positions:

• chr2-147913532-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001616.5(ACVR2A):​c.529-1659G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 151,552 control chromosomes in the GnomAD database, including 11,880 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 0.39 (11880 hom., cov: 30)
• Consequence: ACVR2A NM_001616.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACVR2A	NM_001616.5	c.529-1659G>A		intron_variant		ENST00000241416.12	NP_001607.1
ACVR2A	NM_001278579.2	c.529-1659G>A		intron_variant			NP_001265508.1
ACVR2A	NM_001278580.2	c.205-1659G>A		intron_variant			NP_001265509.1
ACVR2A	XM_047446292.1	c.205-1659G>A		intron_variant			XP_047302248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACVR2A	ENST00000241416.12	c.529-1659G>A		intron_variant		1	NM_001616.5	ENSP00000241416	P1
ACVR2A	ENST00000404590.1	c.529-1659G>A		intron_variant		1		ENSP00000384338	P1
ACVR2A	ENST00000535787.5	c.205-1659G>A		intron_variant		2		ENSP00000439988

Frequencies

GnomAD3 genomes AF: 0.388 AC: 58733 AN: 151434 Hom.: 11867 Cov.: 30

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.392

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.351

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.388 AC: 58784 AN: 151552 Hom.: 11880 Cov.: 30 AF XY: 0.397 AC XY: 29385 AN XY: 74060

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.398

Gnomad4 ASJ AF: 0.284

Gnomad4 EAS AF: 0.380

Gnomad4 SAS AF: 0.508

Gnomad4 FIN AF: 0.553

Gnomad4 NFE AF: 0.423

Gnomad4 OTH AF: 0.356

Alfa AF: 0.413 Hom.: 1681

Bravo AF: 0.365

Asia WGS AF: 0.475 AC: 1651 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.15
DANN	Benign	0.33

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: rs3768688; hg19: chr2-148671101;