rs3820716

Variant names:

• chr2-147922691-G-A
• rs3820716
• NM_001616.5:c.1078-282G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-147922691-G-A
• chr2-147922691-G-T

Variant summary

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

The NM_001616.5(ACVR2A):​c.1078-282G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 151,718 control chromosomes in the GnomAD database, including 17,430 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 0.47 (17430 hom., cov: 31)
• Consequence: ACVR2A NM_001616.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.55
• Publications: 7 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACVR2A	NM_001616.5	c.1078-282G>A		intron_variant	Intron 8 of 10	ENST00000241416.12	NP_001607.1
ACVR2A	NM_001278579.2	c.1078-282G>A		intron_variant	Intron 9 of 11		NP_001265508.1
ACVR2A	NM_001278580.2	c.754-282G>A		intron_variant	Intron 8 of 10		NP_001265509.1
ACVR2A	XM_047446292.1	c.754-282G>A		intron_variant	Intron 8 of 10		XP_047302248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACVR2A	ENST00000241416.12	c.1078-282G>A		intron_variant	Intron 8 of 10	1	NM_001616.5	ENSP00000241416.7
ACVR2A	ENST00000404590.1	c.1078-282G>A		intron_variant	Intron 9 of 11	1		ENSP00000384338.1
ACVR2A	ENST00000535787.5	c.754-282G>A		intron_variant	Intron 8 of 10	2		ENSP00000439988.1

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71700 AN: 151600 Hom.: 17429 Cov.: 31

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.620

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.511

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

GnomAD4 genome AF: 0.473 AC: 71743 AN: 151718 Hom.: 17430 Cov.: 31 AF XY: 0.470 AC XY: 34798 AN XY: 74114

African (AFR) AF: 0.367 AC: 15202 AN: 41384

American (AMR) AF: 0.514 AC: 7824 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.653 AC: 2264 AN: 3466

East Asian (EAS) AF: 0.619 AC: 3183 AN: 5142

South Asian (SAS) AF: 0.466 AC: 2241 AN: 4804

European-Finnish (FIN) AF: 0.427 AC: 4500 AN: 10540

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.513 AC: 34797 AN: 67860

Other (OTH) AF: 0.508 AC: 1070 AN: 2108

Alfa AF: 0.498 Hom.: 8065

Bravo AF: 0.479

Asia WGS AF: 0.481 AC: 1675 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0040
DANN	Benign	0.16
PhyloP100		-2.5
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: rs3820716; hg19: chr2-148680260;